Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

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

Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.

2010-08-04

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a realmore » patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.« less

Spectral Performance of a Composite Single-Crystal Filtered Thermal Neutron Beam for BNCT Research at the University of Missouri

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

J. Brockman; D. W. Nigg; M. F. Hawthorne

2009-07-01

Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The calculated and measured thermal neutron fluxes produced at the irradiation location are 9.6x108 and 8.8x108 neutrons/cm2-s, respectively. Calculated and measured cadmium ratios (Au foils) are 217 and 132. These results indicate a well-thermalized neutron spectrum with sufficient thermal neutron flux formore » a variety of small animal BNCT studies.« less

Investigation on the reflector/moderator geometry and its effect on the neutron beam design in BNCT.

PubMed

Kasesaz, Y; Rahmani, F; Khalafi, H

2015-12-01

In order to provide an appropriate neutron beam for Boron Neutron Capture Therapy (BNCT), a special Beam Shaping Assembly (BSA) must be designed based on the neutron source specifications. A typical BSA includes moderator, reflector, collimator, thermal neutron filter, and gamma filter. In common BSA, the reflector is considered as a layer which covers the sides of the moderator materials. In this paper, new reflector/moderator geometries including multi-layer and hexagonal lattice have been suggested and the effect of them has been investigated by MCNP4C Monte Carlo code. It was found that the proposed configurations have a significant effect to improve the thermal to epithermal neutron flux ratio which is an important neutron beam parameter. Copyright © 2015 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

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

A. Monti Hughes; ECC Pozzi; S. Thorp

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

Accelerator driven neutron source design via beryllium target and 208Pb moderator for boron neutron capture therapy in alternative treatment strategy by Monte Carlo method.

PubMed

Khorshidi, Abdollah

2017-01-01

The reactor has increased its area of application into medicine especially boron neutron capture therapy (BNCT); however, accelerator-driven neutron sources can be used for therapy purposes. The present study aimed to discuss an alternative method in BNCT functions by a small cyclotron with low current protons based on Karaj cyclotron in Iran. An epithermal neutron spectrum generator was simulated with 30 MeV proton energy for BNCT purposes. A low current of 300 μA of the proton beam in spallation target concept via 9Be target was accomplished to model neutron spectrum using 208Pb moderator around the target. The graphite reflector and dual layer collimator were planned to prevent and collimate the neutrons produced from proton interactions. Neutron yield per proton, energy distribution, flux, and dose components in the simulated head phantom were estimated by MCNPX code. The neutron beam quality was investigated by diverse filters thicknesses. The maximum epithermal flux transpired using Fluental, Fe, Li, and Bi filters with thicknesses of 7.4, 3, 0.5, and 4 cm, respectively; as well as the epithermal to thermal neutron flux ratio was 161. Results demonstrated that the induced neutrons from a low energy and low current proton may be effective in tumor therapy using 208Pb moderator with average lethargy and also graphite reflector with low absorption cross section to keep the generated neutrons. Combination of spallation-based BNCT and proton therapy can be especially effective, if a high beam intensity cyclotron becomes available.

Investigating a cyclotron HM-30 based neutron source for BNCT of deep-seated tumors by using shifting method

NASA Astrophysics Data System (ADS)

Suharyana; Riyatun; Octaviana, E. F.

2016-11-01

We have successfully proposed a simulation of a neutron beam-shaping assembly using MCNPX Code. This simulation study deals with designing a compact, optimized, and geometrically simple beam shaping assembly for a neutron source based on a proton cyclotron for BNCT purpose. Shifting method was applied in order to lower the fast neutron energy to the epithermal energy range by choosing appropriate materials. Based on a set of MCNPX simulations, it has been found that the best materials for beam shaping assembly are 3 cm Ni layered with 7 cm Pb as the reflector and 13 cm AlF3 the moderator. Our proposed beam shaping assembly configuration satisfies 2 of 5 of the IAEA criteria, namely the epithermal neutron flux 1.25 × 109 n.cm-2 s-1 and the gamma dose over the epithermal neutron flux is 0.18×10 -13 Gy.cm 2 n -1. However, the ratio of the fast neutron dose rate over neutron epithermal flux is still too high. We recommended that the shifting method must be accompanied by the filter method to reduce the fast neutron flux.

Gamma-Ray Dose Measurement with Radio-Photoluminescence Glass Dosimeter in Mixed Radiation Field for BNCT

NASA Astrophysics Data System (ADS)

Hiramatsu, K.; Yoshihashi, S.; Kusaka, S.; Sato, F.; Hoashi, E.; Murata, I.

2017-09-01

Accelerator based neutron sources (ABNS) are being developed as the next generation neutron irradiation system for BNCT. From the ABNS, unnecessary gamma-rays will be generated by neutron capture reactions, as well as fast neutrons. To control the whole-body radiation dose to the patient, measurement of gamma-ray dose in the irradiation room is necessary. In this study, the objective is to establish a method to measure gamma-ray dose separately in a neutron/gamma mixed field by using RPL glass dosimeter. For this purpose, we proposed a lead filter method which uses a pair of RPL glasses with and without a lead filter outside. In order to realize this method, the basic characteristics of glass dosimeter was verified in the gamma-ray field, before adapting it in the mixture field. From the result of the experiment using the lead filter, the simulation result especially for the case with a lead filter overestimated the absorbed does obtained from measurement. We concluded that the reason of the discrepancy is caused by existence of gradient of the dose distribution in the glass, and the difference of sensitivity to low-energy photon between measurement and theory.

Design of an epithermal column for BNCT based on D D fusion neutron facility

NASA Astrophysics Data System (ADS)

Durisi, E.; Zanini, A.; Manfredotti, C.; Palamara, F.; Sarotto, M.; Visca, L.; Nastasi, U.

2007-05-01

Boron Neutron Capture Therapy (BNCT) is currently performed on patients at nuclear reactors. At the same time the international BNCT community is engaged in the development of alternative facilities for in-hospital treatments. This paper investigates the potential of a novel high-output D-D neutron generator, developed at Lawrence Berkeley National Laboratory (CA, USA), for BNCT. The simulation code MCNP-4C is used to realize an accurate study of the epithermal column in view of the treatment of deep tumours. Different materials and Beam Shaping Assemblies (BSA) are investigated and an optimized configuration is proposed. The neutron beam quality is defined by the standard free beam parameters, calculated averaging over the collimator aperture. The results are discussed and compared with the performances of other facilities.

A feasibility study of a deuterium-deuterium neutron generator-based boron neutron capture therapy system for treatment of brain tumors.

PubMed

Hsieh, Mindy; Liu, Yingzi; Mostafaei, Farshad; Poulson, Jean M; Nie, Linda H

2017-02-01

Boron neutron capture therapy (BNCT) is a binary treatment modality that uses high LET particles to achieve tumor cell killing. Deuterium-deuterium (DD) compact neutron generators have advantages over nuclear reactors and large accelerators as the BNCT neutron source, such as their compact size, low cost, and relatively easy installation. The purpose of this study is to design a beam shaping assembly (BSA) for a DD neutron generator and assess the potential of a DD-based BNCT system using Monte Carlo (MC) simulations. The MC model consisted of a head phantom, a DD neutron source, and a BSA. The head phantom had tally cylinders along the centerline for computing neutron and photon fluences and calculating the dose as a function of depth. The head phantom was placed at 4 cm from the BSA. The neutron source was modeled to resemble the source of our current DD neutron generator. A BSA was designed to moderate and shape the 2.45-MeV DD neutrons to the epithermal (0.5 eV to 10 keV) range. The BSA had multiple components, including moderator, reflector, collimator, and filter. Various materials and configurations were tested for each component. Each BSA layout was assessed in terms of the in-air and in-phantom parameters. The maximum brain dose was limited to 12.5 Gray-Equivalent (Gy-Eq) and the skin dose to 18 Gy-Eq. The optimized BSA configuration included 30 cm of lead for reflector, 45 cm of LiF, and 10 cm of MgF 2 for moderator, 10 cm of lead for collimator, and 0.1 mm of cadmium for thermal neutron filter. Epithermal flux at the beam aperture was 1.0 × 10 5  n epi /cm 2 -s; thermal-to-epithermal neutron ratio was 0.05; fast neutron dose per epithermal was 5.5 × 10 -13  Gy-cm 2 /φ epi , and photon dose per epithermal was 2.4 × 10 -13  Gy-cm 2 /φ epi . The AD, AR, and the advantage depth dose rate were 12.1 cm, 3.7, and 3.2 × 10 -3  cGy-Eq/min, respectively. The maximum skin dose was 0.56 Gy-Eq. The DD neutron yield that is needed to irradiate in reasonable time was 4.9 × 10 13  n/s. Results demonstrated that a DD-based BNCT system could be designed to produce neutron beams that have acceptable in-air and in-phantom characteristics. The parameter values were comparable to those of existing BNCT facilities. Continuing efforts are ongoing to improve the DD neutron yield. © 2016 American Association of Physicists in Medicine.

A Project of Boron Neutron Capture Therapy System based on a Proton Linac Neutron Source

NASA Astrophysics Data System (ADS)

Kiyanagi, Yoshikai; Asano, Kenji; Arakawa, Akihiro; Fukuchi, Shin; Hiraga, Fujio; Kimura, Kenju; Kobayashi, Hitoshi; Kubota, Michio; Kumada, Hiroaki; Matsumoto, Hiroshi; Matsumoto, Akira; Sakae, Takeji; Saitoh, Kimiaki; Shibata, Tokushi; Yoshioka, Masakazu

At present, the clinical trials of Boron Neutron Capture Therapy (BNCT) are being performed at research reactor facilities. However, an accelerator based BNCT has a merit that it can be built in a hospital. So, we just launched a development project for the BNCT based on an accelerator in order to establish and to spread the BNCT as an effective therapy in the near future. In the project, a compact proton linac installed in a hospital will be applied as a neutron source, and energy of the proton beam is planned to be less than about 10 MeV to reduce the radioactivity. The BNCT requires epithermal neutron beam with an intensity of around 1x109 (n/cm2/sec) to deliver the therapeutic dose to a deeper region in a body and to complete the irradiation within an hour. From this condition, the current of the proton beam required is estimated to be a few mA on average. Enormous heat deposition in the target is a big issue. We are aiming at total optimization of the accelerator based BNCT from the linac to the irradiation position. Here, the outline of the project is introduced and the moderator design is presented.

Designing of the 14 MeV neutron moderator for BNCT

NASA Astrophysics Data System (ADS)

Cheng, Dao-Wen; Lu, Jing-Bin; Yang, Dong; Liu, Yu-Min; Wang, Hui-Dong; Ma, Ke-Yan

2012-09-01

In boron neutron capture therapy (BNCT), the ratio of the fast neutron flux to the neutron flux in the tumor (RFNT) must be less than 3%. If a D-T neutron generator is used in BNCT, the 14 MeV neutron moderator must be optimized to reduce the RFNT. Based on the neutron moderation theory and the simulation results, tungsten, lead and diamond were used to moderate the 14 MeV neutrons. Satisfying RFNT of less than 3%, the maximum neutron flux in the tumor was achieved with a three-layer moderator comprised of a 3 cm thick tungsten layer, a 14 cm thick lead layer and a 21 cm thick diamond layer.

Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

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

Zasneda, Sabriani; Widita, Rena

2010-06-22

Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometricalmore » factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.« less

Treatment planning capability assessment of a beam shaping assembly for accelerator-based BNCT.

PubMed

Herrera, M S; González, S J; Burlon, A A; Minsky, D M; Kreiner, A J

2011-12-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) a theoretical study was performed to assess the treatment planning capability of different configurations of an optimized beam shaping assembly for such a facility. In particular this study aims at evaluating treatment plans for a clinical case of Glioblastoma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Study on optimization of multiionization-chamber system for BNCT.

PubMed

Fujii, T; Tanaka, H; Maruhashi, A; Ono, K; Sakurai, Y

2011-12-01

In order to monitor stability of doses from the four components such as thermal, epi-thermal, fast neutron and gamma-ray during BNCT irradiation, we are developing a multiionization-chamber system. This system is consisted of four kinds of ionization chamber, which have specific sensitivity for each component, respectively. Since a suitable structure for each chamber depends on the energy spectrum of the irradiation field, the optimization study of the chamber structures for the epi-thermal neutron beam of cyclotron-based epi-thermal neutron source (C-BENS) was performed by using a Monte Carlo simulation code "PHITS" and suitable chamber-structures were determined. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Monte Carlo model system for core analysis and epithermal neutron beam design at the Washington State University Radiation Center

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

Burns, T.D. Jr.

1996-05-01

The Monte Carlo Model System (MCMS) for the Washington State University (WSU) Radiation Center provides a means through which core criticality and power distributions can be calculated, as well as providing a method for neutron and photon transport necessary for BNCT epithermal neutron beam design. The computational code used in this Model System is MCNP4A. The geometric capability of this Monte Carlo code allows the WSU system to be modeled very accurately. A working knowledge of the MCNP4A neutron transport code increases the flexibility of the Model System and is recommended, however, the eigenvalue/power density problems can be run withmore » little direct knowledge of MCNP4A. Neutron and photon particle transport require more experience with the MCNP4A code. The Model System consists of two coupled subsystems; the Core Analysis and Source Plane Generator Model (CASP), and the BeamPort Shell Particle Transport Model (BSPT). The CASP Model incorporates the S({alpha}, {beta}) thermal treatment, and is run as a criticality problem yielding, the system eigenvalue (k{sub eff}), the core power distribution, and an implicit surface source for subsequent particle transport in the BSPT Model. The BSPT Model uses the source plane generated by a CASP run to transport particles through the thermal column beamport. The user can create filter arrangements in the beamport and then calculate characteristics necessary for assessing the BNCT potential of the given filter want. Examples of the characteristics to be calculated are: neutron fluxes, neutron currents, fast neutron KERMAs and gamma KERMAs. The MCMS is a useful tool for the WSU system. Those unfamiliar with the MCNP4A code can use the MCMS transparently for core analysis, while more experienced users will find the particle transport capabilities very powerful for BNCT filter design.« less

Monte Carlo calculation for the development of a BNCT neutron source (1eV-10KeV) using MCNP code.

PubMed

El Moussaoui, F; El Bardouni, T; Azahra, M; Kamili, A; Boukhal, H

2008-09-01

Different materials have been studied in order to produce the epithermal neutron beam between 1eV and 10KeV, which are extensively used to irradiate patients with brain tumors such as GBM. For this purpose, we have studied three different neutrons moderators (H(2)O, D(2)O and BeO) and their combinations, four reflectors (Al(2)O(3), C, Bi, and Pb) and two filters (Cd and Bi). Results of calculation showed that the best obtained assembly configuration corresponds to the combination of the three moderators H(2)O, BeO and D(2)O jointly to Al(2)O(3) reflector and two filter Cd+Bi optimize the spectrum of the epithermal neutron at 72%, and minimize the thermal neutron to 4% and thus it can be used to treat the deep tumor brain. The calculations have been performed by means of the Monte Carlo N (particle code MCNP 5C). Our results strongly encourage further studying of irradiation of the head with epithermal neutron fields.

An electron linac-based system for BNCT of shallow tumors

NASA Astrophysics Data System (ADS)

Farhad Masoudi, S.; Ghiasi, Hedieh; Harif, Maryam; Rasouli, Fatemeh S.

2018-07-01

Although BNCT has been in existence since the 1950s, it continues to be of special significant and interest for wide groups of researchers. Recent studies, focused on investigating appropriate neutron sources as alternatives for nuclear reactors, revealed the high potential of electron linac-based facilities to improve the efficiency of this treatment method. The present simulation study has been devoted to both designing an optimized and geometrically simple target to be used as a photoneutron source based on an electron linac and designing a configuration composed of arrangement of materials to generate an appropriate beam for BNCT of shallow tumors considering the widely accepted criteria for pre-clinical survey. It has been found that the behavior of photoneutrons' current and their average energy on the surface of the target is independent of the incident energy. Accordingly, we managed to present a formula to predict the average energy of photoneutrons knowing the electron energy to an acceptable approximation avoiding Monte Carlo simulations. Considering the conflict between the beam intensity and its purity in the whole beam designing process, an optimized beam shaping assembly for electron linac of 18 MeV/ mA has been proposed. These results in essence confirm the ability of these sources for BNCT of shallow tumors and are therefore encouraging for further studies. Furthermore, the results show that this configuration, which the corresponding beam fulfills all the medical requirements, is also usable for electron linacs of other energies. This can be of high importance in practical point of view.

INEL BNCT Research Program annual report, 1992

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

Venhuizen, J.R.

1993-05-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1992. Contributions from all the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor targeting compounds, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of biological samples), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potentialmore » toxicity of borocaptate sodium and boronophenylalanine is presented, results of 21 spontaneous-tumor-bearing dogs that have been treated with BNCT at the Brookhaven National Laboratory (BNL) Medical Research Reactor (BMRR) are discussed, and predictions for an epithermal-neutron beam at the Georgia Tech Research Reactor (GTRR) are shown. Cellular-level boron detection and localization by secondary ion mass spectrometry, sputter-initiated resonance ionization spectroscopy, low atomization resonance ionization spectroscopy, and alpha track are presented. Boron detection by ICP-AES is discussed in detail. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors with BNCT is presented. Measurement of the epithermal-neutron flux at BNL and comparison to predictions are shown. Calculations comparing the GTRR and BMRR epithermal-neutron beams are also presented. Individual progress reports described herein are separately abstracted and indexed for the database.« less

Beam shaping assembly optimization for (7)Li(p,n)(7)Be accelerator based BNCT.

PubMed

Minsky, D M; Kreiner, A J

2014-06-01

Within the framework of accelerator-based BNCT, a project to develop a folded Tandem-ElectroStatic-Quadrupole accelerator is under way at the Atomic Energy Commission of Argentina. The proposed accelerator is conceived to deliver a proton beam of 30mA at about 2.5MeV. In this work we explore a Beam Shaping Assembly (BSA) design based on the (7)Li(p,n)(7)Be neutron production reaction to obtain neutron beams to treat deep seated tumors. © 2013 Elsevier Ltd. All rights reserved.

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, W.Y.; Jones, J.L.; Nigg, D.W.; Harker, Y.D.

1999-05-11

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0{times}10{sup 9} neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use. 3 figs.

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, Woo Y.; Jones, James L.; Nigg, David W.; Harker, Yale D.

1999-01-01

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0.times.10.sup.9 neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use.

"Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

2011-04-01

In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma.

PubMed

Yeh, Chun-Nan; Chang, Chi-Wei; Chung, Yi-Hsiu; Tien, Shi-Wei; Chen, Yong-Ren; Chen, Tsung-Wen; Huang, Ying-Cheng; Wang, Hsin-Ell; Chou, You-Cheng; Chen, Ming-Huang; Chiang, Kun-Chun; Huang, Wen-Sheng; Yu, Chung-Shan

2017-09-30

Boron neutron capture therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high-energy helium and alpha particles to kill cancer cells. An optimal response to BNCT depends critically on the time point of maximal 10 B accumulation and highest tumor to normal ratio (T/N) for performing the neutron irradiation. The aggressive cholangiocarcinoma (CCA) representing a liver cancer that overexpresses COX-2 enzyme is aimed to be targeted by COX-2 selective boron carrier, fenbufen boronopinacol (FBPin). Two main works were performed including: 1) chemical synthesis of FBPin as the boron carrier and 2) radiochemical labeling with F-18 to provide the radiofluoro congener, m-[ 18 F]fluorofenbufen ester boronopinacol (m-[ 18 F]FFBPin), to assess the binding affinity, cellular accumulation level and distribution profile in CCA rats. FBPin was prepared from bromofenbufen via 3 steps with 82% yield. The binding assay employed [ 18 F]FFBPin to compete FBPin for binding to COX-1 (IC 50 =0.91±0.68μM) and COX-2 (IC 50 =0.33±0.24μM). [ 18 F]FFBPin-derived 60-min dynamic PET scans predict the 10 B-accumulation of 0.8-1.2ppm in liver and 1.2-1.8ppm in tumor and tumor to normal ratio=1.38±0.12. BNCT was performed 40-55min post intravenous administration of FBPin (20-30mg) in the CCA rats. CCA rats treated with BNCT display more tumor reduction than that by NCT with respect of 2-[ 18 F]fluoro-2-deoxy glucose uptake in the tumor region of interest, 20.83±3.00% (n=12) vs. 12.83±3.79% (n=10), P=0.05. The visualizing agent [ 18 F]FFBPin resembles FBPin to generate the time-dependent boron concentration profile. Optimal neutron irradiation period is thus determinable for BNCT. A boron-substituted agent based on COX-2-binding features has been prepared. The moderate COX-2/COX-1 selectivity index of 2.78 allows a fair tumor selectivity index of 1.38 with a mild cardiovascular effect. The therapeutic effect from FBPin with BNCT warrants a proper COX-2 targeting of boron NSAIDs. Copyright © 2017. Published by Elsevier B.V.

Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT).

PubMed

Kageji, T; Mizobuchi, Y; Nagahiro, S; Nakagawa, Y; Kumada, H

2014-06-01

The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68Gy(w) and 44Gy(w), respectively. Copyright © 2014. Published by Elsevier Ltd.

“Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

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

Ana J. Molinari; Emiliano C. C. Pozzi; Andrea Monti Hughes

In the present study we evaluated the therapeutic effect and/or potential radiotoxicity of the novel “Tandem” Boron Neutron Capture Therapy (T-BNCT) for the treatment of oral cancer in the hamster cheek pouch model at RA-3 Nuclear Reactor. Two groups of animals were treated with “Tandem BNCT”, i.e. BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (T-24h-BNCT) or 48 h (T-48h-BNCT) later. A total tumor dose-matched single application of BNCT mediated by BPA and GB-10 administered jointly [(BPA + GB-10)-BNCT] was administered to an additional group of animals. At 28 days post-treatment, T-24h-BNCTmore » and T-48h-BNCT induced, respectively, overall tumor control (OTC) of 95% and 91%, with no statistically significant differences between protocols. Tumor response for the single application of (BPA + GB-10)-BNCT was 75%, significantly lower than for T-BNCT. The T-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47% and 60% of the animals respectively. No normal tissue radiotoxicity was associated to tumor control for any of the protocols. “Tandem” BNCT enhances tumor control in oral cancer and reduces or, at worst, does not increase, mucositis in dose-limiting precancerous tissue.« less

Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

PubMed

Brandão, S F; Campos, T P R

2015-07-01

This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

Design of photon converter and photoneutron target for High power electron accelerator based BNCT.

PubMed

Rahmani, Faezeh; Seifi, Samaneh; Anbaran, Hossein Tavakoli; Ghasemi, Farshad

2015-12-01

An electron accelerator, ILU-14, with current of 10 mA and 100 kW in power has been considered as one of the options for neutron source in Boron Neutron Capture Therapy (BNCT). The final design of neutron target has been obtained using MCNPX to optimize the neutron production. Tungsten in strip shape and D2O in cylindrical form have been proposed as the photon converter and the photoneutron target, respectively. In addition calculation of heat deposition in the photon target design has been considered to ensure mechanical stability of target. The results show that about 8.37×10(12) photoneutron/s with average energy of 615 keV can be produced by this neutron source design. In addition, using an appropriate beam shaping assembly an epithermal neutron flux of the order of 1.24×10(8) cm(-2) s(-1) can be obtained for BNCT applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design of thermal neutron beam based on an electron linear accelerator for BNCT.

PubMed

Zolfaghari, Mona; Sedaghatizadeh, Mahmood

2016-12-01

An electron linear accelerator (Linac) can be used for boron neutron capture therapy (BNCT) by producing thermal neutron flux. In this study, we used a Varian 2300 C/D Linac and MCNPX.2.6.0 code to simulate an electron-photoneutron source for use in BNCT. In order to decelerate the produced fast neutrons from the photoneutron source, which optimize the thermal neutron flux, a beam-shaping assembly (BSA) was simulated. After simulations, a thermal neutron flux with sharp peak at the beam exit was obtained in the order of 3.09×10 8 n/cm 2 s and 6.19×10 8 n/cm 2 s for uranium and enriched uranium (10%) as electron-photoneutron sources respectively. Also, in-phantom dose analysis indicates that the simulated thermal neutron beam can be used for treatment of shallow skin melanoma in time of about 85.4 and 43.6min for uranium and enriched uranium (10%) respectively. Copyright © 2016. Published by Elsevier Ltd.

Epithermal neutron formation for boron neutron capture therapy by adiabatic resonance crossing concept

NASA Astrophysics Data System (ADS)

Khorshidi, A.; Ghafoori-Fard, H.; Sadeghi, M.

2014-05-01

Low-energy protons from the cyclotron in the range of 15-30 MeV and low current have been simulated on beryllium (Be) target with a lead moderator around the target. This research was accomplished to design an epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) using the moderated neutron on the average produced from 9Be target via (p, xn) reaction in Adiabatic Resonance Crossing (ARC) concept. Generation of neutron to proton ratio, energy distribution, flux and dose components in head phantom have been simulated by MCNP5 code. The reflector and collimator were designed in prevention and collimation of derivation neutrons from proton bombarding. The scalp-skull-brain phantom consisting of bone and brain equivalent material has been simulated in order to evaluate the dosimetric effect on the brain. Results of this analysis demonstrated while the proton energy decreased, the dose factor altered according to filters thickness. The maximum epithermal flux revealed using fluental, Fe and bismuth (Bi) filters with thicknesses of 9.4, 3 and 2 cm, respectively and also the epithermal to thermal neutron flux ratio was 103.85. The potential of the ARC method to replace or complement the current reactor-based supply sources of BNCT purposes.

Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

PubMed Central

Brandão, S F

2015-01-01

Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

Exploring Boron Neutron Capture Therapy for non-small cell lung cancer.

PubMed

Farías, Rubén O; Bortolussi, Silva; Menéndez, Pablo R; González, Sara J

2014-12-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high LET radiation. It consists in the enrichment of tumour with (10)B and in the successive irradiation of the target with low energy neutrons producing charged particles that mainly cause non-repairable damages to the cells. The feasibility to treat Non Small Cells Lung Cancer (NSCLC) with BNCT was explored. This paper proposes a new approach to determine treatment plans, introducing the possibility to choose the irradiation start and duration to maximize the tumour dose. A Tumour Control Probability (TCP) suited for lung BNCT as well as other high dose radiotherapy schemes was also introduced. Treatment plans were evaluated in localized and disseminated lung tumours. Semi-ideal and real energy spectra beams were employed to assess the best energy range and the performance of non-tailored neutron sources for lung tumour treatments. The optimal neutron energy is within [500 eV-3 keV], lower than the 10 keV suggested for the treatment of deep-seated tumours in the brain. TCPs higher than 0.6 and up to 0.95 are obtained for all cases. Conclusions drawn from [Suzuki et al., Int Canc Conf J 1 (4) (2012) 235-238] supporting the feasibility of BNCT for shallow lung tumours are confirmed, however discussions favouring the treatment of deeper lesions and disseminated disease are also opened. Since BNCT gives the possibility to deliver a safe and potentially effective treatment for NSCLC, it can be considered a suitable alternative for patients with few or no treatment options. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

PubMed

Molinari, Ana J; Thorp, Silvia I; Portu, Agustina M; Saint Martin, Gisela; Pozzi, Emiliano C C; Heber, Elisa M; Bortolussi, Silva; Itoiz, Maria E; Aromando, Romina F; Monti Hughes, Andrea; Garabalino, Marcela A; Altieri, Saverio; Trivillin, Verónica A; Schwint, Amanda E

2015-01-01

We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval.

PubMed

Monti Hughes, Andrea; Pozzi, Emiliano C C; Heber, Elisa M; Thorp, Silvia; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Molinari, Ana J; Garabalino, Marcela A; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2011-11-01

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10+BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10+BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

SERA -- An advanced treatment planning system for neutron therapy and BNCT

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

Nigg, D.W.; Wemple, C.A.; Wessol, D.E.

1999-09-01

Detailed treatment planning calculations on a patient-specific basis are required for boron neutron capture therapy (BNCT). Two integrated treatment planning systems developed specifically for BNCT have been in clinical use in the United States over the past few years. The MacNCTPLAN BNCT treatment planning system is used in the clinical BNCT trials that are underway at the Massachusetts Institute of Technology. A second system, BNCT{_}rtpe (BNCT radiation therapy planning environment), developed independently by the Idaho national Engineering and Environmental Laboratory (INEEL) in collaboration with Montana State University (MSU), is used for treatment planning in the current series of BNCT clinicalmore » trials for glioblastoma at Brookhaven National Laboratory (BNL). This latter system is also licensed for use at several other BNCT research facilities worldwide. Although the currently available BNCT planning systems have served their purpose well, they suffer from somewhat long computation times (2 to 3 CPU-hours or more per field) relative to standard photon therapy planning software. This is largely due to the need for explicit three-dimensional solutions to the relevant transport equations. The simplifying approximations that work well for photon transport computations are not generally applicable to neutron transport computations. Greater computational speeds for BNCT treatment planning must therefore generally be achieved through the application of improved numerical techniques rather than by simplification of the governing equations. Recent efforts at INEEL and MSU have been directed toward this goal. This has resulted in a new paradigm for this type of calculation and the subsequent creation of the new simulation environment for radiotherapy applications (SERA) treatment planning system for BNCT. SERA is currently in initial clinical testing in connection with the trials at BNL, and it is expected to replace the present BNCT{_}rtpe system upon general release during 1999.« less

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

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

Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For eachmore » rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.« less

Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

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

Andrea Monti Hughes; Emiliano C.C. Pozzi; Elisa M. Heber

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT);more » (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.« less

An update on the clinical trial of BNCT at the BMRR

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

Ma, R.; Capala, J.; Chanana, A.D.

1999-09-01

Boron neutron capture therapy (BNCT) was proposed more than six decades ago. It is a binary treatment modality that requires selective delivery of a {sup 10}B-labeled compound to a tumor and slow neutron irradiation of the tumor-bearing tissues. In order to improve the penetration of the neutron beam, an epithermal neutron beam was developed at the Brookhaven Medical Research Reactor (BMRR). This epithermal neutron beam can deliver relatively high thermal neutron fluence at depth without severe skin damage. Boronophenylalanine-fructose (BPA-F), a nontoxic boron carrier, was found to preferentially accumulate in tumor cells following intravenous infusion in patients with GBM. Inmore » preclinical BNCT studies in rats bearing 9L gliosarcoma, BPA-mediated BNCT was shown to be more efficacious than photon irradiation. In 1994, improvements in the neutron beam and in the understanding of the radiobiology of BPA-mediated BNCT led to the initiation of BNCT trials for human GBM at BMRR using BPA-F and epithermal neutrons. The primary objective of the phase I/II clinical trial of BPA-mediated BNCT at BMRR is to evaluate the safety of the BPA-F-mediated BNCT using epithermal neutrons in patients with GBM at a series of escalating BNCT doses. An incidental objective is to evaluate the therapeutic effectiveness of BNCT at each dose level. For each dose escalation group, the average brain dose (ABD) is escalated, as well as the minimum tumor dose. In summary, the BNCT procedure employed in the phase I/II clinical trial of BPA-F-mediated BNCT for GBM at BNL was found to be safe in all patients. The palliation afforded by a single session of BNCT compares favorably with palliation provided by fractionated photon therapy and adjuvant chemotherapy. If no evidence of radiation-induced brain toxicity is found in the current protocol, BNCT radiation dose will be further escalated.« less

Building of scientific information system for sustainable development of BNCT in Bulgaria.

PubMed

Mitev, M; Ilieva, K; Apostolov, T

2009-07-01

Building a boron neutron capture therapy (BNCT) facility is foreseen within the reconstruction of the Research Reactor IRT (IRT) of the Institute for Nuclear Research and Nuclear Energy of the Bulgaria Academy of Sciences (INRNE). The development of BNCT at IRT plays a very significant role in the plan for sustainable application of the reactor. A centralized scientific information system on BNCT is being built at the INRNE with the purpose to collect and sort new information as knowledge accumulated during more than thirty years history of BNCT. This BNCT information system will help the creation and consolidation of a well informed and interconnected interdisciplinary team of physicists, chemists, biologists, and radio-oncologists for establishing BNCT cancer treatment in Bulgaria. It will strengthen more intensive development of the national network as well as its enlargement to the Balkan region countries. Furthermore, to acquaint the public at large with the opportunity for BNCT cancer treatment will be addressed. Human, social, and economics results due to BNCT for many patients from Balkan region are expected.

A novel design of beam shaping assembly to use D-T neutron generator for BNCT.

PubMed

Kasesaz, Yaser; Karimi, Marjan

2016-12-01

In order to use 14.1MeV neutrons produced by d-T neutron generators, two special and novel Beam Shaping Assemblies (BSA), including multi-layer and hexagonal lattice have been suggested and the effect of them has been investigated by MCNP4C Monte Carlo code. The results show that the proposed BSA can provide the qualified epithermal neutron beam for BNCT. The final epithermal neutron flux is about 6e9 n/cm2.s. The final proposed BSA has some different advantages: 1) it consists of usual and well-known materials (Pb, Al, Fluental and Cd); 2) it has a simple geometry; 3) it does not need any additional gamma filter; 4) it can provide high flux of epithermal neutrons. As this type of neutron source is under development in the world, it seems that they can be used clinically in a hospital considering the proposed BSA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats.

PubMed

Pozzi, Emiliano C C; Trivillin, Verónica A; Colombo, Lucas L; Monti Hughes, Andrea; Thorp, Silvia I; Cardoso, Jorge E; Garabalino, Marcela A; Molinari, Ana J; Heber, Elisa M; Curotto, Paula; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Schwint, Amanda E

2013-11-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential.

PubMed

Heber, Elisa M; Kueffer, Peter J; Lee, Mark W; Hawthorne, M Frederick; Garabalino, Marcela A; Molinari, Ana J; Nigg, David W; Bauer, William; Hughes, Andrea Monti; Pozzi, Emiliano C C; Trivillin, Verónica A; Schwint, Amanda E

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

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

David W. Nigg

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1)more » MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.« less

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

Wessol, D.E.; Wheeler, F.J.; Babcock, R.S.

Several improvements have been developed for the BNCT radiation treatment planning environment (BNCT-Rtpe) during 1994. These improvements have been incorporated into Version 1.0 of BNCT-Rtpe which is currently installed at the INEL, BNL, Japanese Research Center (JRC), and Finland`s Technical Research Center. Platforms supported by this software include Hewlett-Packard (HP), SUN, International Business Machines (IBM), and Silicon Graphics Incorporated (SGI). A draft version of the BNCT-Rtpe user manual is available. Version 1.1 of BNCT-Rtpe is scheduled for release in March 1995. It is anticipated that Version 2.x of BNCT-Rtpe, which includes the nonproprietary NURBS library and data structures, will bemore » released in September 1995.« less

Performance characteristics of the MIT fission converter based epithermal neutron beam.

PubMed

Riley, K J; Binns, P J; Harling, O K

2003-04-07

A pre-clinical characterization of the first fission converter based epithermal neutron beam (FCB) designed for boron neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered beam were confirmed from neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal neutron flux is accompanied by very low specific photon and fast neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.

Simulating variable source problems via post processing of individual particle tallies

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

Bleuel, D.L.; Donahue, R.J.; Ludewigt, B.A.

2000-10-20

Monte Carlo is an extremely powerful method of simulating complex, three dimensional environments without excessive problem simplification. However, it is often time consuming to simulate models in which the source can be highly varied. Similarly difficult are optimization studies involving sources in which many input parameters are variable, such as particle energy, angle, and spatial distribution. Such studies are often approached using brute force methods or intelligent guesswork. One field in which these problems are often encountered is accelerator-driven Boron Neutron Capture Therapy (BNCT) for the treatment of cancers. Solving the reverse problem of determining the best neutron source formore » optimal BNCT treatment can be accomplished by separating the time-consuming particle-tracking process of a full Monte Carlo simulation from the calculation of the source weighting factors which is typically performed at the beginning of a Monte Carlo simulation. By post-processing these weighting factors on a recorded file of individual particle tally information, the effect of changing source variables can be realized in a matter of seconds, instead of requiring hours or days for additional complete simulations. By intelligent source biasing, any number of different source distributions can be calculated quickly from a single Monte Carlo simulation. The source description can be treated as variable and the effect of changing multiple interdependent source variables on the problem's solution can be determined. Though the focus of this study is on BNCT applications, this procedure may be applicable to any problem that involves a variable source.« less

Development of a tandem-electrostatic-quadrupole accelerator facility for BNCT.

PubMed

Kreiner, A J; Thatar Vento, V; Levinas, P; Bergueiro, J; Di Paolo, H; Burlon, A A; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Minsky, D M; Estrada, L; Hazarabedian, A; Johann, F; Suarez Sandin, J C; Castell, W; Davidson, J; Davidson, M; Giboudot, Y; Repetto, M; Obligado, M; Nery, J P; Huck, H; Igarzabal, M; Fernandez Salares, A

2009-07-01

In this work we describe the present status of an ongoing project to develop a tandem-electrostatic-quadrupole (TESQ) accelerator facility for accelerator-based (AB) BNCT at the Atomic Energy Commission of Argentina in Buenos Aires. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction slightly beyond its resonance at 2.25 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the (7)Li(p,n)(7)Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. An electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT. The machine being designed and constructed is a folded TESQ with a high-voltage terminal at 1.2 MV intended to work in air. Such a machine is conceptually shown to be capable of transporting and accelerating a 30 mA proton beam to 2.4 MeV. The general geometric layout, its associated electrostatic fields, and the acceleration tube are simulated using a 3D finite element procedure. The design and construction of the ESQ modules is discussed and their electrostatic fields are investigated. Beam transport calculations through the accelerator are briefly mentioned. Likewise, work related to neutron production targets, strippers, beam shaping assembly and patient treatment room is briefly described.

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor.

PubMed

Monti Hughes, Andrea; Longhino, Juan; Boggio, Esteban; Medina, Vanina A; Martinel Lamas, Diego J; Garabalino, Marcela A; Heber, Elisa M; Pozzi, Emiliano C C; Itoiz, María E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2017-11-01

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model.

PubMed

Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Thorp, Silvia; Monti Hughes, Andrea; Molinari, Ana J; Garabalino, Marcela A; Heber, Elisa M; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Trivillin, Verónica A; Schwint, Amanda E

2012-08-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT, boronophenylalanine (BPA) + neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA-BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks post-treatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA-BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mg fell significantly to 19 ± 16 mg for BPA-BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA-BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA-BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

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

David W. Nigg

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8more » for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.« less

Boron neutron capture therapy: Moving toward targeted cancer therapy.

PubMed

Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

2016-01-01

Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

Feasibility study on the use of uranium in photoneutron target and BSA optimization for Linac based BNCT

NASA Astrophysics Data System (ADS)

Rahmani, Faezeh; Shahriari, Majid; Minoochehr, Abdolhamid; Nedaie, Hasan

2011-06-01

A hybrid photoneutron target including natural uranium has been studied for a 20 MeV linear electron accelerator (Linac) based Boron Neutron Capture Therapy (BNCT) facility. In this study the possibility of using uranium to increase the neutron intensity has been investigated by focusing on the time dependence behavior of the build-up and decay of the delayed gamma rays from fission fragments and activation products through photo-fission reactions in the BSA (Beam Shaping Assembly) configuration design. Delayed components of neutrons and photons were calculated. The obtained BSA parameters are in agreement with the IAEA recommendation and compared to the hybrid photoneutron target without U. The epithermal flux in the suggested design is 2.67E9 (n/cm 2s/mA).

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment.

PubMed

Kageji, Teruyoshi; Nagahiro, Shinji; Mizobuchi, Yoshifumi; Matsuzaki, Kazuhito; Nakagawa, Yoshinobu; Kumada, Hiroaki

2014-01-01

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases

PubMed Central

2014-01-01

Background and importance Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Clinical presentation Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. Conclusion BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients. PMID:24387301

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

PubMed

Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

2.5 MeV CW 4-vane RFQ accelerator design for BNCT applications

NASA Astrophysics Data System (ADS)

Zhu, Xiaowen; Wang, Hu; Lu, Yuanrong; Wang, Zhi; Zhu, Kun; Zou, Yubin; Guo, Zhiyu

2018-03-01

Boron Neutron Capture Therapy (BNCT) promises a bright future in cancer therapy for its highly selective destruction of cancer cells, using the 10B +n→7Li +4 He reaction. It offers a more satisfactory therapeutic effect than traditional methods for the treatment of malignant brain tumors, head and neck cancer, melanoma, liver cancer and so on. A CW 4-vane RFQ, operating at 162.5 MHz, provides acceleration of a 20 mA proton beam to 2.5 MeV, bombarding a liquid lithium target for neutron production with a soft neutron energy spectrum. The fast neutron yield is about 1.73×1013 n/s. We preliminarily develop and optimize a beam shaping assembly design for the 7Li(p, n)7Be reaction with a 2.5 MeV proton beam. The epithermal neutron flux simulated at the beam port will reach up to 1 . 575 ×109 n/s/cm2. The beam dynamics design, simulation and benchmark for 2.5 MeV BNCT RFQ have been performed with both ParmteqM (V3.05) and Toutatis, with a transmission efficiency higher than 99.6% at 20 mA. To ease the thermal management in the CW RFQ operation, we adopt a modest inter-vane voltage design (U = 65 kV), though this does increase the accelerator length (reaching 5.2 m). Using the well-developed 3D electromagnetic codes, CST MWS and ANSYS HFSS, we are able to deal with the complexity of the BNCT RFQ, taking the contribution of each component in the RF volume into consideration. This allows us to optimize the longitudinal field distribution in a full-length model. Also, the parametric modeling technique is of great benefit to extensive modifications and simulations. In addition, the resonant frequency tuning of this RFQ is studied, giving the tuning sensitivities of vane channel and wall channel as -16.3 kHz/°C and 12.4 kHz/°C, respectively. Finally, both the multipacting level of this RFQ and multipacting suppressing in the coaxial coupler are investigated.

[Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

PubMed

Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

2015-01-01

Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

DEVELOPMENT OF A MULTIMODAL MONTE CARLO BASED TREATMENT PLANNING SYSTEM.

PubMed

Kumada, Hiroaki; Takada, Kenta; Sakurai, Yoshinori; Suzuki, Minoru; Takata, Takushi; Sakurai, Hideyuki; Matsumura, Akira; Sakae, Takeji

2017-10-26

To establish boron neutron capture therapy (BNCT), the University of Tsukuba is developing a treatment device and peripheral devices required in BNCT, such as a treatment planning system. We are developing a new multimodal Monte Carlo based treatment planning system (developing code: Tsukuba Plan). Tsukuba Plan allows for dose estimation in proton therapy, X-ray therapy and heavy ion therapy in addition to BNCT because the system employs PHITS as the Monte Carlo dose calculation engine. Regarding BNCT, several verifications of the system are being carried out for its practical usage. The verification results demonstrate that Tsukuba Plan allows for accurate estimation of thermal neutron flux and gamma-ray dose as fundamental radiations of dosimetry in BNCT. In addition to the practical use of Tsukuba Plan in BNCT, we are investigating its application to other radiation therapies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy (BNCT) facility: application to the treatment of experimental oral cancer.

PubMed

Pozzi, E; Nigg, D W; Miller, M; Thorp, S I; Heber, E M; Zarza, L; Estryk, G; Monti Hughes, A; Molinari, A J; Garabalino, M; Itoiz, M E; Aromando, R F; Quintana, J; Trivillin, V A; Schwint, A E

2009-07-01

The National Atomic Energy Commission of Argentina (CNEA) constructed a novel thermal neutron source for use in boron neutron capture therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The aim of the present study was to perform a dosimetric characterization of the facility and undertake radiobiological studies of BNCT in an experimental model of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x 10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1), indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10-BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters were treated similarly to evaluate normal tissue radiotoxicity. The total physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5 Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue radiotoxicity. Significant but reversible mucositis in precancerous tissue surrounding tumors was associated to BPA-BNCT. The therapeutic success of different BNCT protocols in treating experimental oral cancer at this novel facility was unequivocally demonstrated.

Final Stage in the Design of a Boron Neutron Capture Therapy facility at CEADEN, Cuba

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

Cabal, F. Padilla; Martin, G.

A neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, the therapeutic gain and the neutron fluence are utilized as beam assessment parameters. An irradiation cavity is used instead of a parallel beam port for the therapy. Calculations are performed using the MCNP5 code. After the optimization of our beam-shaper a study of the dose distribution in the head, neck, tyroids, lungs and upper and middle spine had been made. The therapeutic gain is increased whilemore » the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT.« less

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

PubMed Central

Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model.

PubMed

Lin, Sy-Yu; Lin, Chen-Jou; Liao, Jiunn-Wang; Peir, Jinn-Jer; Chen, Wei-Lin; Chi, Chin-Wen; Lin, Yung-Chang; Liu, Yu-Ming; Chou, Fong-In

2013-11-01

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

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

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

NASA Astrophysics Data System (ADS)

Sakurai, Yoshinori; Tanaka, Hiroki; Takata, Takushi; Fujimoto, Nozomi; Suzuki, Minoru; Masunaga, Shinichiro; Kinashi, Yuko; Kondo, Natsuko; Narabayashi, Masaru; Nakagawa, Yosuke; Watanabe, Tsubasa; Ono, Koji; Maruhashi, Akira

2015-07-01

At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world's first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics.

An Overview on the Developments and Improvements of a Treatment Planning System for BNCT

NASA Astrophysics Data System (ADS)

Cerullo, N.; Daquino, G. G.; Muzi, L.

2006-06-01

Boron Neutron Capture Therapy (BNCT) is a radiation therapy for cancer that employs a neutron beam and a /sup 10/B-loaded drug to selectively kill tumor cells whilst sparing surrounding healthy tissues (HT). In conventional radiation therapy, treatment planning systems (TPSs) implementing simplified models of radiation transport and dose deposition allow to efficiently optimize all the relevant parameters prior to the patient's irradiation. This simplified approach is not feasible in BNCT, because the presence of neutrons requires the use of more complex radiation transport models. For this reason, current BNCT TPSs routinely perform several radiation transport simulations based on the Monte Carlo method. Our team has been involved in BNCT TPS research since 1996, introducing the original trait of employing in the simulation a three-dimensional map of the highly heterogeneous boron distribution in tissues, obtained through PET scanning of the target region. This approach differs markedly from the standard one, in which boron concentration is assumed to be uniform in each "macro region" within the patient's head, and its value is estimated on the basis of blood sampling. The first result of this research was the prototype software CARONTE, employed to test the feasibility of the new approach and to carry out a comparative study by applying the two different approaches to the same test case. The results, presented in this paper in terms of the computed physical dose rate due to the /sup 10/B reaction, show how the different assumptions made in the two approaches can significantly influence important TP parameters. This led to the development of Boron Distribution TP Software (BDTPS), an original and complete TPS. The different phases of the experimental validation of BDTPS, which included the design and construction of an ad hoc phantom able to host a number of vials loaded with /sup 10/B solutions, is presented here. The phantom, which subsequently underwent computed tomography (CT) and positron emission tomography (PET) scanning, was irradiated in the High Flux Reactor (HFR) at JRC, Petten, The Netherlands.

Accelerator-based BNCT.

PubMed

Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

2014-06-01

The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases. © 2013 Elsevier Ltd. All rights reserved.

Small Accelerators for the Next Generation of BNCT Irradiation Systems

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

Kobayashi, T.; Tanaka, K.; Bengua, G.

2005-01-15

The neutron irradiation system for boron neutron capture therapy (BNCT) using compact accelerators installed at hospitals was mainly investigated for the usage of direct neutrons from near-threshold {sup 7}Li(p,n){sup 7}Be, and moderated neutrons from 2.5 MeV {sup 7}Li(p,n){sup 7}Be reactions and other reactions. This kind of system can supply the medical doctors and patients with convenience to carry out BNCT in hospitals. The accelerator system would be regarded as the next-generation of BNCT in the near future.

Development of a multi-modal Monte-Carlo radiation treatment planning system combined with PHITS

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

Kumada, Hiroaki; Nakamura, Takemi; Komeda, Masao

A new multi-modal Monte-Carlo radiation treatment planning system is under development at Japan Atomic Energy Agency. This system (developing code: JCDS-FX) builds on fundamental technologies of JCDS. JCDS was developed by JAEA to perform treatment planning of boron neutron capture therapy (BNCT) which is being conducted at JRR-4 in JAEA. JCDS has many advantages based on practical accomplishments for actual clinical trials of BNCT at JRR-4, the advantages have been taken over to JCDS-FX. One of the features of JCDS-FX is that PHITS has been applied to particle transport calculation. PHITS is a multipurpose particle Monte-Carlo transport code, thus applicationmore » of PHITS enables to evaluate doses for not only BNCT but also several radiotherapies like proton therapy. To verify calculation accuracy of JCDS-FX with PHITS for BNCT, treatment planning of an actual BNCT conducted at JRR-4 was performed retrospectively. The verification results demonstrated the new system was applicable to BNCT clinical trials in practical use. In framework of R and D for laser-driven proton therapy, we begin study for application of JCDS-FX combined with PHITS to proton therapy in addition to BNCT. Several features and performances of the new multimodal Monte-Carlo radiotherapy planning system are presented.« less

Boron Neutron Capture Therapy for Malignant Brain Tumors

PubMed Central

MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

Boron Neutron Capture Therapy for Malignant Brain Tumors.

PubMed

Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

2016-07-15

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

PubMed

Haapaniemi, Aaro; Kankaanranta, Leena; Saat, Riste; Koivunoro, Hanna; Saarilahti, Kauko; Mäkitie, Antti; Atula, Timo; Joensuu, Heikki

2016-05-01

To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

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

Haapaniemi, Aaro, E-mail: aaro.haapaniemi@hus.fi; Kankaanranta, Leena; Saat, Riste

2016-05-01

Purpose: To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Methods and Materials: Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patientsmore » who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. Results: Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. Conclusions: Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.« less

Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

PubMed

Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

2015-12-01

Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antitumor effect of boron nitride nanotubes in combination with thermal neutron irradiation on BNCT.

PubMed

Nakamura, Hiroyuki; Koganei, Hayato; Miyoshi, Tatsuro; Sakurai, Yoshinori; Ono, Koji; Suzuki, Minoru

2015-01-15

The first BNCT antitumor effects of BNNTs toward B16 melanoma cells were demonstrated. The use of DSPE-PEG2000 was effective for preparation of the BNNT-suspended aqueous solution. BNNT-DSPE-PEG2000 accumulated in B16 melanoma cells approximately three times higher than BSH and the higher BNCT antitumor effect was observed in the cells treated with BNNT-DSPE-PEG2000 compared to those treated with BSH, indicating that BNNT-DSPE-PEG2000 would be a possible candidate as a boron delivery vehicle for BNCT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

PubMed Central

2010-01-01

Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [60Co] γ-rays (P < 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (P < 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased. Conclusions Compared with γ-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2. PMID:21122152

Basic requirements and parameter optimization for boron neutron capture therapy of extracorporeal irradiated and auto-transplanted organs.

PubMed

Wortmann, Birgit; Knorr, Jürgen

2012-08-01

In 2001 and 2003, at the University of Pavia, Italy, boron neutron capture therapy (BNCT) has been successfully used in the treatment of hepatic colorectal metastases (Pinelli et al., 2002; Zonta et al., 2006). The treatment procedure (TAOrMINA protocol) is characterised by the auto-transplantation and extracorporeal irradiation of the liver using a thermal neutron beam. The clinical use of this approach requires well founded data and an optimized irradiation facility. In order to start with this work and to decide upon its feasibility at the research reactor TRIGA Mainz, basic data and requirements have been considered (Wortmann, 2008). Computer calculations using the ATTILA (Transpire Inc. 2006) and MCNP (LANL, 2005) codes have been performed, including data from conventional radiation therapy, from the TAOrMINA approach, resulting in reasonable estimations. Basic data and requirements and optimal parameters have been worked out, especially for use at an optimized TRIGA irradiation facility (Wortmann, 2008). Advantages of the extracorporeal irradiation with auto-transplantation and the potential of an optimized irradiation facility could be identified. Within the requirements, turning the explanted organ over by 180° appears preferable to a whole side source, similar to a permanent rotation of the organ. The design study and the parameter optimization confirm the potential of this approach to treat metastases in explanted organs. The results do not represent actual treatment data but a first estimation. Although all specific values refer to the TRIGA Mainz, they may act as a useful guide for other types of neutron sources. The recommended modifications (Wortmann, 2008) show the suitability of TRIGA reactors as a radiation source for BNCT of extracorporeal irradiated and auto-transplanted organs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.

PubMed

Monti Hughes, A; Pozzi, Ecc; Thorp, S I; Curotto, P; Medina, V A; Martinel Lamas, D J; Rivera, E S; Garabalino, M A; Farías, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Nigg, D W; Trivillin, V A; Schwint, A E

2015-09-01

Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels.

PubMed

Yang, C H; Lin, Y T; Hung, Y H; Liao, J W; Peir, J J; Liu, H M; Lin, Y L; Liu, Y M; Chen, Y W; Chuang, K S; Chou, F I

2015-12-01

Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

PubMed

Fujimoto, T; Andoh, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Sonobe, H; Epstein, Alan L; Akisue, T; Kirihata, M; Kurosaka, M; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

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

Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan

Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60more » mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.« less

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

PubMed

Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

2014-06-01

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Boron Neutron Capture Therapy - A Literature Review

PubMed Central

Nedunchezhian, Kavitaa; Thiruppathy, Manigandan; Thirugnanamurthy, Sarumathi

2016-01-01

Boron Neutron Capture Therapy (BNCT) is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation. BNCT bestows upon the nuclear reaction that occurs when Boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield α particles (Helium-4) and recoiling lithium-7 nuclei. A large number of 10 Boron (10B) atoms have to be localized on or within neoplastic cells for BNCT to be effective, and an adequate number of thermal neutrons have to be absorbed by the 10B atoms to maintain a lethal 10B (n, α) lithium-7 reaction. The most exclusive property of BNCT is that it can deposit an immense dose gradient between the tumour cells and normal cells. BNCT integrates the fundamental focusing perception of chemotherapy and the gross anatomical localization proposition of traditional radiotherapy. PMID:28209015

Perspectives of boron-neutron capture therapy of malignant brain tumors

NASA Astrophysics Data System (ADS)

Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

2017-09-01

Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

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

Albertson, B.; Binney, S.

This paper describes research on the following: the structure of {sup 10}B{sub 10}-ovine corticotropin releasing hormone and {sup 10}B{sub 10}-growth hormone releasing hormone; the BNCT effect on AtT-20 cell {sup 10}B{sub 10}-CRH incubations in vitro; BNCT effects on GH{sub 4}C{sub 1} cell {sup 10}B{sub 10} growth hormone releasing factor incubation in vitro; and competitive inhibition of AtT-20 cell BNCT effect.

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro.

PubMed

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

2013-08-06

Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma.

A feasibility study of the Tehran research reactor as a neutron source for BNCT.

PubMed

Kasesaz, Yaser; Khalafi, Hossein; Rahmani, Faezeh; Ezati, Arsalan; Keyvani, Mehdi; Hossnirokh, Ashkan; Shamami, Mehrdad Azizi; Monshizadeh, Mahdi

2014-08-01

Investigation on the use of the Tehran Research Reactor (TRR) as a neutron source for Boron Neutron Capture Therapy (BNCT) has been performed by calculating and measuring energy spectrum and the spatial distribution of neutrons in all external irradiation facilities, including six beam tubes, thermal column, and the medical room. Activation methods with multiple foils and a copper wire have been used for the mentioned measurements. The results show that (1) the small diameter and long length beam tubes cannot provide sufficient neutron flux for BNCT; (2) in order to use the medical room, the TRR core should be placed in the open pool position, in this situation the distance between the core and patient position is about 400 cm, so neutron flux cannot be sufficient for BNCT; and (3) the best facility which can be adapted for BNCT application is the thermal column, if all graphite blocks can be removed. The epithermal and fast neutron flux at the beginning of this empty column are 4.12×10(9) and 1.21×10(9) n/cm(2)/s, respectively, which can provide an appropriate neutron beam for BNCT by designing and constructing a proper Beam Shaping Assembly (BSA) structure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.

PubMed

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-06-01

Bevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases

PubMed Central

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-01-01

Background Bevacizumab, an anti–vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Methods Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. Results The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Conclusions Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas. PMID:23460324

Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map

PubMed Central

2013-01-01

Background Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT. Methods The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models. Results Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models. Conclusions The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis. PMID:23915330

Boron neutron capture therapy for recurrent high-grade meningiomas.

PubMed

Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Ono, Koji; Miyatake, Shin-Ichi

2013-10-01

Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.

Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumors of the hamster cheek pouch.

PubMed

Aromando, Romina F; Trivillin, Verónica A; Heber, Elisa M; Pozzi, Emiliano; Schwint, Amanda E; Itoiz, María E

2010-05-01

Mast cell (MC) activation in the hamster cheek pouch cancerization model is associated with the increase in tumor cell proliferation, mediated in turn by tryptase, a protease released from mast cell granules after activation. Tryptase induces tumor cell proliferation through the activation of PAR-2 (protease activated receptor-2) on the plasma membrane of carcinoma cells. The therapeutic success of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) in tumor control in the hamster cheek pouch oral cancer model has been previously reported by our laboratory. Early effects of BPA-BNCT on tumors of the hamster cheek pouch include a reduction in DNA-synthesis with the concomitant decrease in the proliferation of malignant cells. The aim of the present study was to investigate the early histological changes in mast cells after BPA-BNCT in tumors and premalignant tissue of the hamster cheek pouch. Tumor-bearing pouches were treated with BPA-BNCT or beam only (neutron irradiation without prior administration of the boron compound) and sacrificed 1day after treatment. The samples were fixed in Carnoy fixative and stained with alcian blue-safranin to identify all the populations of mast cells. Total, active and inactive mast cells (MC) were counted in the connective tissue and the adventitious tissue underlying the pouch wall and at the base of the tumors in pouches treated with BPA-BNCT, in keeping with a previously described technique. BPA-BNCT induced a marked reduction in the total number of mast cells in the pouch (p<0.05). This reduction in the total number of mast cells was due to a reduction in mast cells at the base of the tumor (p<0.005) and it occurred at the expense of the active mast cells (p<0.05). A slight reduction that did not reach statistical significance also occurred in the amount of mast cells in the pouch wall (that corresponds to the premalignant tissue in tumor-bearing pouches), and in the adventitious tissue. In this case the reduction was seen in the inactive population. Both BPA-BNCT and beam only elicited a qualitative change in the secretion modality of the granule content. Although further studies are needed to evaluate the subcellular effect of BNCT on mast cell granule secretion, the reduction in cell proliferation induced by BPA-BNCT would be partially due to the decrease in total mast cells in the hamster check pouch. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong-In; Yang, Chia-Min; Lin, Chun-Cheng

2013-09-01

A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02594b

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Opportunities afforded by the intense nanosecond neutron pulses from a plasma focus source for neutron capture therapy and the preliminary simulation results

NASA Astrophysics Data System (ADS)

Giannini, G.; Gribkov, V.; Longo, F.; Ramos Aruca, M.; Tuniz, C.

2012-11-01

The use of short and powerful neutron pulses for boron neutron capture therapy (BNCT) can potentially increase selectivity and reduce the total dose absorbed by the patient. The biological effects of radiation depend on the dose, the dose power and the spatial distribution of the microscopic energy deposition. A dense plasma focus (DPF) device emits very short (in the nanosecond range) and extremely intense pulses of fast neutrons (2.5 or 14 MeV neutrons—from D-D or D-T nuclear reactions) and x-rays. Optimal spectra of neutrons formed for use in BNCT must contain an epithermal part to ensure a reasonable penetration depth into tissues at high enough cross-section on boron. So the powerful nanosecond pulses of fast neutrons generated by DPF must be moderated. After this moderation, the pulse duration must be shorter compared with the duration of the reaction with free radicals, that is, ⩾1 μs. In this work we focus on the development of a detailed simulation of interaction of short-pulse radiation from a DPF with the device's materials and with different types of moderators to estimate the dose power at the cells for this dynamic case. The simulation was carried out by means of the Geant4 toolkit in two main steps: the modeling of the pulsed neutron source device itself; the study of the interaction of fast mono-energetic neutrons with a moderator specific for BNCT.

Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

PubMed

Seki, Ryoichi; Wakisaka, Yushi; Morimoto, Nami; Takashina, Masaaki; Koizumi, Masahiko; Toki, Hiroshi; Fukuda, Mitsuhiro

2017-12-01

The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

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

D. W. Nigg

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in themore » hamster cheek pouch model of oral cancer.« less

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

PubMed

Garabalino, Marcela A; Monti Hughes, Andrea; Molinari, Ana J; Heber, Elisa M; Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Nievas, Susana; Nigg, David W; Aromando, Romina F; Itoiz, Maria E; Trivillin, Verónica A; Schwint, Amanda E

2011-03-01

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3. © Springer-Verlag 2010

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

PubMed Central

Sköld, K; Gorlia, T; Pellettieri, L; Giusti, V; H-Stenstam, B; Hopewell, J W

2010-01-01

The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier l-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O6-methylguanine–DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. PMID:20603410

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

PubMed Central

Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

2012-01-01

Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

PubMed Central

2013-01-01

Background Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. Methods The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. Results The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Conclusions Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma. PMID:23915425

Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

PubMed

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

PubMed Central

HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

2015-01-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.

PubMed

Sasai, Masao; Nakamura, Hiroyuki; Sougawa, Nagako; Sakurai, Yoshinori; Suzuki, Minoru; Lee, Chun Man

2016-03-01

Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells. In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model. HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT. Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

Nigg, D.W.; Mitchell, H.E.; Harker, Y.D.

Therapeutically-useful epithermal-neutron beams for BNCT are currently generated by nuclear reactors. Various accelerator-based neutron sources for BNCT have been proposed and some low intensity prototypes of such sources, generally featuring the use of proton beams and beryllium or lithium targets have been constructed. This paper describes an alternate approach to the realization of a clinically useful accelerator-based source of epithermal neutrons for BNCT that reconciles the often conflicting objectives of target cooling, neutron beam intensity, and neutron beam spectral purity via a two stage photoneutron production process.

INEEL BNCT research program. Annual report, January 1, 1996--December 31, 1996

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

Venhuizen, J.R.

1997-04-01

This report is a summary of the progress and research produced for the Idaho National Engineering and Environmental Laboratory (INEEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1996. Contributions from the individual investigators about their projects are included, specifically, physics: treatment planning software, real-time neutron beam measurement dosimetry, measurement of the Finnish research reactor epithermal neutron spectrum, BNCT accelerator technology; and chemistry: analysis of biological samples and preparation of {sup 10}B enriched decaborane.

Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

PubMed

Hattori, Yoshihide; Kusaka, Shintaro; Mukumoto, Mari; Ishimura, Miki; Ohta, Yoichiro; Takenaka, Hiroshi; Uehara, Kouki; Asano, Tomoyuki; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji; Tanimori, Shinji; Kirihata, Mitsunori

2014-12-01

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

FLUKA simulation studies on in-phantom dosimetric parameters of a LINAC-based BNCT

NASA Astrophysics Data System (ADS)

Ghal-Eh, N.; Goudarzi, H.; Rahmani, F.

2017-12-01

The Monte Carlo simulation code, FLUKA version 2011.2c.5, has been used to estimate the in-phantom dosimetric parameters for use in BNCT studies. The in-phantom parameters of a typical Snyder head, which are necessary information prior to any clinical treatment, have been calculated with both FLUKA and MCNPX codes, which exhibit a promising agreement. The results confirm that FLUKA can be regarded as a good alternative for the MCNPX in BNCT dosimetry simulations.

Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

PubMed

Achilli, Cesare; Grandi, Stefania; Ciana, Annarita; Guidetti, Gianni F; Malara, Alessandro; Abbonante, Vittorio; Cansolino, Laura; Tomasi, Corrado; Balduini, Alessandra; Fagnoni, Maurizio; Merli, Daniele; Mustarelli, Piercarlo; Canobbio, Ilaria; Balduini, Cesare; Minetti, Giampaolo

2014-04-01

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies. © 2014.

Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

PubMed Central

Miyatake, Shin-Ichi; Kawabata, Shinji; Nonoguchi, Naosuke; Yokoyama, Kunio; Kuroiwa, Toshihiko; Matsui, Hideki; Ono, Koji

2009-01-01

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT. PMID:19289492

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

PubMed Central

2011-01-01

Background Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the 10B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require 10B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues. Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration. In this study, we developed a novel vector for 10B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events. Methods We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors in vivo, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors. Results CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher 10B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (p < 0.05). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher 10B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of 10B. Conclusion CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues. PMID:21247507

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

PubMed Central

Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Toledo Arruda-Neto, João Dias; Maria-Engler, Silvya Stuchi; Tiago, Manoela; Capelozzi, Vera Luiza; Giorgi, Ricardo Rodrigues; Maria, Durvanei Augusto

2013-01-01

Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and 7Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT. PMID:23527236

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components.

PubMed

Moghaddasi, Leyla; Bezak, Eva

2018-03-01

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.

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

Laramore, G.E.; Griffin, B.R.; Spence, A.

The purpose of this work is to establish and maintain a database for patients from the United States who have received BNCT in Japan for malignant gliomas of the brain. This database will serve as a resource for the DOE to aid in decisions relating to BNCT research in the United States, as well as assisting the design and implementation of clinical trials of BNCT for brain cancer patients in this country. The database will also serve as an information resource for patients with brain tumors and their families who are considering this form of therapy.

The neutron flux monitors from 20 keV to 1 MeV for BNCT: performance study using accelerator-based neutron sources

NASA Astrophysics Data System (ADS)

Guan, X. C.; Gong, Y.; Murata, I.; Wang, T. S.

2018-05-01

The performance of the neutron flux monitors from 20 keV to 1 MeV developed for boron neutron capture therapy (BNCT) is studied by Monte Carlo simulations using accelerator-based neutron sources (ABNSs). The results show that the performance of the neutron flux monitors is very satisfactory and they can be efficiently used in practical applications to measure the neutron fluxes from 20 keV to 1 MeV of ABNSs for BNCT to high accuracy.

Tandem-ESQ for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT)

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

Kreiner, A. J.; Escuela de Ciencia y Tecnologia, Universidad de Gral San Martin; CONICET,

2007-02-12

A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed as a machine for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT). The machine is shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep seated tumors in less than an hour.

A critical assessment of boron target compounds for boron neutron capture therapy.

PubMed

Hawthorne, M Frederick; Lee, Mark W

2003-01-01

Boron neutron capture therapy (BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme (GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron-10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron-10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB-10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new (and existing) boron target candidates at all stages of their development and the large-scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study demonstrating improved efficacy is completed. Eventually, BNCT in some form will be commercialized.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).

PubMed

Henriksson, Roger; Capala, Jacek; Michanek, Annika; Lindahl, Sten-Ake; Salford, Leif G; Franzén, Lars; Blomquist, Erik; Westlin, Jan-Erik; Bergenheim, A Tommy

2008-08-01

To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

PubMed

Wang, Ling-Wei; Liu, Yen-Wan Hsueh; Chou, Fong-In; Jiang, Shiang-Huei

2018-06-19

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

Design of a beam shaping assembly and preliminary modelling of a treatment room for accelerator-based BNCT at CNEA.

PubMed

Burlon, A A; Girola, S; Valda, A A; Minsky, D M; Kreiner, A J; Sánchez, G

2011-12-01

This work reports on the characterisation of a neutron beam shaping assembly (BSA) prototype and on the preliminary modelling of a treatment room for BNCT within the framework of a research programme for the development and construction of an accelerator-based BNCT irradiation facility in Buenos Aires, Argentina. The BSA prototype constructed has been characterised by means of MCNP simulations as well as a set of experimental measurements performed at the Tandar accelerator at the National Atomic Energy Commission of Argentina. Copyright © 2011 Elsevier Ltd. All rights reserved.

Conceptual design of BNCT facility based on the TRR medical room

NASA Astrophysics Data System (ADS)

Golshanian, M.; Rajabi, A. A.; Kasesaz, Y.

2017-10-01

This paper presents a conceptual design of the Boron Neutron Capture Therapy (BNCT) facility based on the medical room of Tehran Research Reactor (TRR). The medical room is located behind the east wall of the reactor pool. The designed beam line is an in-pool Beam Shaping Assembly (BSA) which is considered between the reactor core and the medical room wall. The final designed BSA can provide 2.96× 109 n/cm2ṡs epithermal neutron flux at the irradiation position with acceptable beam contamination to use as a clinical BNCT.

Progress In The Development Of A Tomographic SPECT System For Online Dosimetry In BNCT

NASA Astrophysics Data System (ADS)

Minsky, D. M.; Valda, A.; Kreiner, A. J.; Burlon, A. A.; Green, S.; Wojnecki, C.; Ghani, Z.

2010-08-01

In boron neutron capture therapy (BNCT) the delivered dose to the patient depends both on the neutron beam characteristics and on the 10B body distribution which, in turn, is governed by the tumor specificity of the 10B drug-carrier. BNCT dosimetry is a complex matter due to the several interactions that neutrons can undergo with the different nuclei present in tissue. However the boron capture reaction 10B(n,α)7Li accounts for about 80 % of the total dose in a tumor with 40 ppm in 10B concentration. Present dosimetric methods are indirect, based on drug biodistribution statistical data and subjected to inter and intra-patient variability. In order to overcome the consequences of the concomitant high dosimetric uncertainties, we propose a SPECT (Single Photon Emission Tomography) approach based on the detection of the prompt gamma-ray (478 keV) emitted in 94 % of the cases from 7Li. For this purpose we designed, built and tested a prototype based on LaBr3(Ce) scintillators. Measurements on a head and tumor phantom were performed in the accelerator-based BNCT facility of the University of Birmingham (UK). They result in the first tomographic image of the 10B capture distribution obtained in a BNCT facility.

"Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

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

Ana J. Molinari; Andrea Monti Hughes; Elisa M. Heber

2011-04-01

Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with a thermal or epithermal neutron beam. The minor abundance stable isotope of boron, 10B, interacts with low energy (thermal) neutrons to produce high linear energy transfer (LET) a-particles and 7Li ions. These disintegration products are known to have a high relative biological effectiveness (RBE). Their short range (<10 {micro}m) would limit the damage to cells containing 10B (1,2). Thus, BNCT would target tumor tissue selectively, sparing normal tissue. Clinical trials of BNCT for the treatment ofmore » glioblastoma multiforme and/or melanoma and, more recently, head and neck tumors and liver metastases, using boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborane (BSH) as the 10B carriers, have been performed or are underway in Argentina, Japan, the US and Europe (e.g. 3-8). To date, the clinical results have shown a potential, albeit inconclusive, therapeutic advantage for this technique. Contributory translational studies have been carried out employing a variety of experimental models based on the implantation of tumor cells in normal tissue (e.g. 5).« less

Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

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

Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari

2011-03-01

Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studiesmore » at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.« less

Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.

PubMed

Yu, Haiyan; Tang, Xiaobin; Shu, Diyun; Liu, Yuanhao; Geng, Changran; Gong, Chunhui; Hang, Shuang; Chen, Da

2017-03-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

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

Subhash Chandra

2008-05-30

The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysismore » of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.« less

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

PubMed

Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

2017-01-23

Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma. We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED. In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant. Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2012-01-01

Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by usemore » of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.« less

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience.

PubMed

Bortolussi, Silva; Postuma, Ian; Protti, Nicoletta; Provenzano, Lucas; Ferrari, Cinzia; Cansolino, Laura; Dionigi, Paolo; Galasso, Olimpio; Gasparini, Giorgio; Altieri, Saverio; Miyatake, Shin-Ichi; González, Sara J

2017-08-15

Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator. The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison. The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy. The possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery.

Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

NASA Astrophysics Data System (ADS)

Sztejnberg Goncalves-Carralves, Manuel Leonardo

This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT for HER2+ breast cancers for deep seated tumors using MITRII-FCB facility with an 8 cm diameter beam (port closest-to-tumor position), with boron concentrations in the tumor higher than 32 mug/g, and for a tumor-to-healthy tissue boron concentration ratio of 8:1. The therapeutic ratios for the proposed treatment would be higher than five for skin and adipose tissue and higher than three for tumor surrounding fibroglandular tissue. The microdosimetry study shows potential improvements in the therapeutic ratios based on the expected sub-cellular boron biodistributions. The engineering simulation study of clinical cases shows the advantages of using BNCT for HER+ breast cancers. Assuming an assured high efficiency of the boron agent delivery, the proposed concept can be considered for stage IV HER2+ breast cancers in treating the metastasized tumors in brain, head and neck, and lungs.

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

PubMed

Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

2015-12-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases.

PubMed

Trivillin, V A; Garabalino, M A; Colombo, L L; González, S J; Farías, R O; Monti Hughes, A; Pozzi, E C C; Bortolussi, S; Altieri, S; Itoiz, M E; Aromando, R F; Nigg, D W; Schwint, A E

2014-06-01

BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25-76ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung. © 2013 Published by Elsevier Ltd.

Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

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

D.W. Nigg; Various Others

BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer.

PubMed

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-Ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-Ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

Progress In The Development Of A Tomographic SPECT System For Online Dosimetry In BNCT

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

Minsky, D. M.; Kreiner, A. J.; ECyT, UNSAM, M. de Irigoyen 3100

2010-08-04

In boron neutron capture therapy (BNCT) the delivered dose to the patient depends both on the neutron beam characteristics and on the {sup 10}B body distribution which, in turn, is governed by the tumor specificity of the {sup 10}B drug-carrier. BNCT dosimetry is a complex matter due to the several interactions that neutrons can undergo with the different nuclei present in tissue. However the boron capture reaction {sup 10}B(n,{alpha}){sup 7}Li accounts for about 80 % of the total dose in a tumor with 40 ppm in {sup 10}B concentration. Present dosimetric methods are indirect, based on drug biodistribution statistical datamore » and subjected to inter and intra-patient variability. In order to overcome the consequences of the concomitant high dosimetric uncertainties, we propose a SPECT (Single Photon Emission Tomography) approach based on the detection of the prompt gamma-ray (478 keV) emitted in 94 % of the cases from {sup 7}Li. For this purpose we designed, built and tested a prototype based on LaBr{sub 3}(Ce) scintillators. Measurements on a head and tumor phantom were performed in the accelerator-based BNCT facility of the University of Birmingham (UK). They result in the first tomographic image of the 10B capture distribution obtained in a BNCT facility.« less

INEL BNCT Program

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

Ackermann, A.L.

1991-08-01

This Bulletin presents a summary of accomplishments and highlights in the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for August 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

Measurement of in-phantom neutron flux and gamma dose in Tehran research reactor boron neutron capture therapy beam line.

PubMed

Bavarnegin, Elham; Sadremomtaz, Alireza; Khalafi, Hossein; Kasesaz, Yaser

2016-01-01

Determination of in-phantom quality factors of Tehran research reactor (TRR) boron neutron capture therapy (BNCT) beam. The doses from thermal neutron reactions with 14N and 10B are calculated by kinetic energy released per unit mass approach, after measuring thermal neutron flux using neutron activation technique. Gamma dose is measured using TLD-700 dosimeter. Different dose components have been measured in a head phantom which has been designed and constructed for BNCT purpose in TRR. Different in-phantom beam quality factors have also been determined. This study demonstrates that the TRR BNCT beam line has potential for treatment of superficial tumors.

Epithermal neutron beam for BNCT research at Washington State University

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

Venhuizen, J.R.; Nigg, D.W.; Wheeler, F.J.

1999-09-01

Veterinary radiation oncology researchers at the Washington State University (WSU) School of Veterinary Medicine have made major contributions to the understanding of the in-vivo radiobiology of boron neutron capture therapy (BNCT) over the years. Recent attention has been focused on the development of a more convenient and cost-effective local epithermal-neutron beam facility for BNCT research and boronated pharmaceutical screening in large-animal models at WSU. The design of such a facility, to be installed in the thermal column region of the TRIGA research reactor at WSU, was performed in a collaborative effort of SWU and the Idaho National Engineering and Environmentalmore » Laboratory. Construction is now underway.« less

Radiation shielding evaluation of the BNCT treatment room at THOR: a TORT-coupled MCNP Monte Carlo simulation study.

PubMed

Chen, A Y; Liu, Y-W H; Sheu, R J

2008-01-01

This study investigates the radiation shielding design of the treatment room for boron neutron capture therapy at Tsing Hua Open-pool Reactor using "TORT-coupled MCNP" method. With this method, the computational efficiency is improved significantly by two to three orders of magnitude compared to the analog Monte Carlo MCNP calculation. This makes the calculation feasible using a single CPU in less than 1 day. Further optimization of the photon weight windows leads to additional 50-75% improvement in the overall computational efficiency.

Boron-containing amino carboxylic acid compounds and uses thereof

DOEpatents

Kabalka, George W.; Srivastava, Rajiv R.

2000-03-14

Novel compounds which are useful for boron neutron capture therapy (BNCT) are disclosed. The compounds comprise a stable boron-containing group and an aminocycloalkane carboxylic acid group or a boronated acyclic hydrocarbon-linked amino carboxylic acid. Methods for synthesis of the compounds and for use of the compounds in BNCT are disclosed.

INEL BNCT Program: Volume 5, No. 9

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

Ackermann, A.L.

1991-01-01

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

Gyrotron-driven high current ECR ion source for boron-neutron capture therapy neutron generator

NASA Astrophysics Data System (ADS)

Skalyga, V.; Izotov, I.; Golubev, S.; Razin, S.; Sidorov, A.; Maslennikova, A.; Volovecky, A.; Kalvas, T.; Koivisto, H.; Tarvainen, O.

2014-12-01

Boron-neutron capture therapy (BNCT) is a perspective treatment method for radiation resistant tumors. Unfortunately its development is strongly held back by a several physical and medical problems. Neutron sources for BNCT currently are limited to nuclear reactors and accelerators. For wide spread of BNCT investigations more compact and cheap neutron source would be much more preferable. In present paper an approach for compact D-D neutron generator creation based on a high current ECR ion source is suggested. Results on dense proton beams production are presented. A possibility of ion beams formation with current density up to 600 mA/cm2 is demonstrated. Estimations based on obtained experimental results show that neutron target bombarded by such deuteron beams would theoretically yield a neutron flux density up to 6·1010 cm-2/s. Thus, neutron generator based on a high-current deuteron ECR source with a powerful plasma heating by gyrotron radiation could fulfill the BNCT requirements significantly lower price, smaller size and ease of operation in comparison with existing reactors and accelerators.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer

PubMed Central

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted. PMID:23955053

The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.

PubMed

Michiue, Hiroyuki; Sakurai, Yoshinori; Kondo, Natsuko; Kitamatsu, Mizuki; Bin, Feng; Nakajima, Kiichiro; Hirota, Yuki; Kawabata, Shinji; Nishiki, Tei-ichi; Ohmori, Iori; Tomizawa, Kazuhito; Miyatake, Shin-ichi; Ono, Koji; Matsui, Hideki

2014-03-01

New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

PubMed Central

MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

2014-01-01

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

Neutron medical treatment of tumours — a survey of facilities

NASA Astrophysics Data System (ADS)

Wagner, F. M.; Loeper-Kabasakal, B.; Breitkreutz, H.

2012-03-01

Neutron therapy has two branches: Fast Neutron Therapy (FNT) and Boron Neutron Capture Therapy (BNCT). The mean neutron energies used for FNT range from 2 MeV to 25 MeV whereas the maximum energy for BNCT is about 10 keV. Neutron generators for FNT have been cyclotrons, accelerators and reactors, whereas BNCT is so far bound to reactors. Both therapies use the effects of high-LET radiation (secondary recoil protons and alpha particles, respectively) and can attack otherwise radioresistant tumours, however, with the hazard of adverse effects for irradiated healthy tissue. FNT has been administered to about 30,000 patients world-wide. From formerly 40 facilities, only eight are operational or stand-by today. The reasons for this development have been, on the one hand, related to technical and economical conditions; on the other hand, strong side effects and insufficient proof of clinical results in the early years as well as increasing competition with new clinical methods have reduced patient numbers. In fact, strict observations of indications, appropriate therapy-planning including low-LET radiation, and consequent treatment of side effects have lead to remarkable results in the meantime. BNCT initially was developed for the treatment of extremely aggressive forms of brain tumour, taking advantage of the action of the blood-brain-barrier which allows for a boronated compound to be selectively enriched in tumour cells. Meanwhile, also malignant melanoma (MM) and Head-and-Neck (H&T) tumours are treated because of their relative radioresistance. At present, epithermal beams with sufficient flux are available only at two facilities. Existing research reactors were indispensable in the development of BNCT, but are to be replaced by hospital-based epithermal neutron sources. Clinical results indicate significantly increased survival times, but the number of patients ever treated is still below 1,000. 3D-dose calculation systems have been developed at several facilities and guarantee a high safety for both therapies, FNT and BNCT.

Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

PubMed

Hashimoto, Y; Hiraga, F; Kiyanagi, Y

2015-12-01

We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

INEL BNCT Program: Volume 5, No. 9. Bulletin, September 1991

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

Ackermann, A.L.

1991-12-31

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory`s (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

Progress on the accelerator based SPES-BNCT project at INFN Legnaro

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

Esposito, J.; Colautti, P.; Pisent, A.

2007-02-12

In the framework of an advanced Exotic Ion Beam facility, named SPES (Study and Production of Exotic Species), that will allow a frontier program both in nuclear and interdisciplinary physics, an intense thermal neutron beam facility, devoted to perform Boron Neutron Capture Therapy (BNCT) experimental treatments on skin melanoma tumor, is currently under construction based on the SPES proton driver. A vast radiobiological investigation in vitro and in vivo has started with the new 10B carriers developed. Special microdosimetric detectors have been constructed to properly measure all the BNCT dose components and their qualities. Both microdosimetric and radiobiological measurements aremore » being performed at the new HYTHOR beam shaping assembly at the Enea-Casaccia TAPIRO reactor.« less

Dose factor entry and display tool for BNCT radiotherapy

DOEpatents

Wessol, Daniel E.; Wheeler, Floyd J.; Cook, Jeremy L.

1999-01-01

A system for use in Boron Neutron Capture Therapy (BNCT) radiotherapy planning where a biological distribution is calculated using a combination of conversion factors and a previously calculated physical distribution. Conversion factors are presented in a graphical spreadsheet so that a planner can easily view and modify the conversion factors. For radiotherapy in multi-component modalities, such as Fast-Neutron and BNCT, it is necessary to combine each conversion factor component to form an effective dose which is used in radiotherapy planning and evaluation. The Dose Factor Entry and Display System is designed to facilitate planner entry of appropriate conversion factors in a straightforward manner for each component. The effective isodose is then immediately computed and displayed over the appropriate background (e.g. digitized image).

Measurement and simulation of the TRR BNCT beam parameters

NASA Astrophysics Data System (ADS)

Bavarnegin, Elham; Sadremomtaz, Alireza; Khalafi, Hossein; Kasesaz, Yaser; Golshanian, Mohadeseh; Ghods, Hossein; Ezzati, Arsalan; Keyvani, Mehdi; Haddadi, Mohammad

2016-09-01

Recently, the configuration of the Tehran Research Reactor (TRR) thermal column has been modified and a proper thermal neutron beam for preclinical Boron Neutron Capture Therapy (BNCT) has been obtained. In this study, simulations and experimental measurements have been carried out to identify the BNCT beam parameters including the beam uniformity, the distribution of the thermal neutron dose, boron dose, gamma dose in a phantom and also the Therapeutic Gain (TG). To do this, the entire TRR structure including the reactor core, pool, the thermal column and beam tubes have been modeled using MCNPX Monte Carlo code. To measure in-phantom dose distribution a special head phantom has been constructed and foil activation techniques and TLD700 dosimeter have been used. The results show that there is enough uniformity in TRR thermal BNCT beam. TG parameter has the maximum value of 5.7 at the depth of 1 cm from the surface of the phantom, confirming that TRR thermal neutron beam has potential for being used in treatment of superficial brain tumors. For the purpose of a clinical trial, more modifications need to be done at the reactor, as, for example design, and construction of a treatment room at the beam exit which is our plan for future. To date, this beam is usable for biological studies and animal trials. There is a relatively good agreement between simulation and measurement especially within a diameter of 10 cm which is the dimension of usual BNCT beam ports. This relatively good agreement enables a more precise prediction of the irradiation conditions needed for future experiments.

Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.

PubMed

Sato, Tatsuhiko; Masunaga, Shin-Ichiro; Kumada, Hiroaki; Hamada, Nobuyuki

2018-01-17

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10 B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations. In the model, the probability density of the absorbed doses in microscopic scales is the fundamental physical index for characterizing the radiation fields. A new computational method was established to determine the probability density for application to BNCT using the Particle and Heavy Ion Transport code System PHITS. The parameters used in the model were determined from the measured surviving fraction of tumor cells administrated with two kinds of 10 B compounds. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. The model can predict the biological effectiveness of newly developed 10 B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas

PubMed Central

2013-01-01

Background Boron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of 10B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice. Materials and methods Tumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation. Results The 10B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT. Conclusions These results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels. PMID:24295213

Microdosimetric evaluation of the neutron field for BNCT at Kyoto University reactor by using the PHITS code.

PubMed

Baba, H; Onizuka, Y; Nakao, M; Fukahori, M; Sato, T; Sakurai, Y; Tanaka, H; Endo, S

2011-02-01

In this study, microdosimetric energy distributions of secondary charged particles from the (10)B(n,α)(7)Li reaction in boron-neutron capture therapy (BNCT) field were calculated using the Particle and Heavy Ion Transport code System (PHITS). The PHITS simulation was performed to reproduce the geometrical set-up of an experiment that measured the microdosimetric energy distributions at the Kyoto University Reactor where two types of tissue-equivalent proportional counters were used, one with A-150 wall alone and another with a 50-ppm-boron-loaded A-150 wall. It was found that the PHITS code is a useful tool for the simulation of the energy deposited in tissue in BNCT based on the comparisons with experimental results.

An Accelerator Neutron Source for BNCT

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

Blue, Thomas, E

2006-03-14

The overall goal of this project was to develop an accelerator-based neutron source (ABNS) for Boron Neutron Capture Therapy (BNCT). Specifically, our goals were to design, and confirm by measurement, a target assembly and a moderator assembly that would fulfill the design requirements of the ABNS. These design requirements were 1) that the neutron field quality be as good as the neutron field quality for the reactor-based neutron sources for BNCT, 2) that the patient treatment time be reasonable, 3) that the proton current required to treat patients in reasonable times be technologially achievable at reasonable cost with good reliability,more » and accelerator space requirements which can be met in a hospital, and finally 4) that the treatment be safe for the patients.« less

Evaluation of the effective dose during BNCT at TRR thermal column epithermal facility.

PubMed

Jarahi, Hossein; Kasesaz, Yaser; Saleh-Koutahi, Seyed Mohsen

2016-04-01

An epithermal neutron beam has been designed for Boron neutron Capture Therapy (BNCT) at the thermal column of Tehran Research Reactor (TRR) recently. In this paper the whole body effective dose, as well as the equivalent doses of several organs have been calculated in this facility using MCNP4C Monte Carlo code. The effective dose has been calculated by using the absorbed doses determined for each individual organ, taking into account the radiation and tissue weighting factors. The ICRP 110 whole body male phantom has been used as a patient model. It was found that the effective dose during BNCT of a brain tumor is equal to 0.90Sv. This effective dose may induce a 4% secondary cancer risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Near threshold ⁷Li(p,n) ⁷Be reaction as neutron source for BNCT.

PubMed

Minsky, D M; Kreiner, A J

2015-12-01

(7)Li(p,n)(7)Be is an endothermic reaction and working near its threshold (1.88 MeV) has the advantage of neutron spectra with maximum energies of about 100 keV, considerably lower than at higher beam energies, or than using other neutron-producing reactions or as for the uranium fission spectrum, relevant for BNCT based on nuclear reactors. With this primary energy it is much easier to obtain the energies needed for treating deep seated tumors by BNCT (about 10 keV). This work studies bombarding energies up to 2.05 MeV, different beam incidence angles and the effect of the undesirable gamma production via the (7)Li(p,γp') (7)Li reaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Triple ionization chamber method for clinical dose monitoring with a Be-covered Li BNCT field.

PubMed

Nguyen, Thanh Tat; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Nguyen, Chien Cong; Endo, Satoru

2016-11-01

Fast neutron, gamma-ray, and boron doses have different relative biological effectiveness (RBE). In boron neutron capture therapy (BNCT), the clinical dose is the total of these dose components multiplied by their RBE. Clinical dose monitoring is necessary for quality assurance of the irradiation profile; therefore, the fast neutron, gamma-ray, and boron doses should be separately monitored. To estimate these doses separately, and to monitor the boron dose without monitoring the thermal neutron fluence, the authors propose a triple ionization chamber method using graphite-walled carbon dioxide gas (C-CO 2 ), tissue-equivalent plastic-walled tissue-equivalent gas (TE-TE), and boron-loaded tissue-equivalent plastic-walled tissue-equivalent gas [TE(B)-TE] chambers. To use this method for dose monitoring for a neutron and gamma-ray field moderated by D 2 O from a Be-covered Li target (Be-covered Li BNCT field), the relative sensitivities of these ionization chambers are required. The relative sensitivities of the TE-TE, C-CO 2 , and TE(B)-TE chambers to fast neutron, gamma-ray, and boron doses are calculated with the particle and heavy-ion transport code system (PHITS). The relative sensitivity of the TE(B)-TE chamber is calculated with the same method as for the TE-TE and C-CO 2 chambers in the paired chamber method. In the Be-covered Li BNCT field, the relative sensitivities of the ionization chambers to fast neutron, gamma-ray, and boron doses are calculated from the kerma ratios, mass attenuation coefficient tissue-to-wall ratios, and W-values. The Be-covered Li BNCT field consists of neutrons and gamma-rays which are emitted from a Be-covered Li target, and this resultant field is simulated by using PHITS with the cross section library of ENDF-VII. The kerma ratios and mass attenuation coefficient tissue-to-wall ratios are determined from the energy spectra of neutrons and gamma-rays in the Be-covered Li BNCT field. The W-value is calculated from recoil charged particle spectra by the collision of neutrons and gamma-rays with the wall and gas materials of the ionization chambers in the gas cavities of TE-TE, C-CO 2 , and TE(B)-TE chambers ( 10 B concentrations of 10, 50, and 100 ppm in the TE-wall). The calculated relative sensitivity of the C-CO 2 chamber to the fast neutron dose in the Be-covered Li BNCT field is 0.029, and those of the TE-TE and TE(B)-TE chambers are both equal to 0.965. The relative sensitivities of the C-CO 2 , TE-TE, and TE(B)-TE chambers to the gamma-ray dose in the Be-covered Li BNCT field are all 1 within the 1% calculation uncertainty. The relative sensitivities of TE(B)-TE to boron dose with concentrations of 10, 50, and 100 ppm 10 B are calculated to be 0.865 times the ratio of the in-tumor to in-chamber wall boron concentration. The fast neutron, gamma-ray, and boron doses of a tumor in-air can be separately monitored by the triple ionization chamber method in the Be-covered Li BNCT field. The results show that these doses can be easily converted to the clinical dose with the depth correction factor in the body and the RBE.

On optimal infinite impulse response edge detection filters

NASA Technical Reports Server (NTRS)

Sarkar, Sudeep; Boyer, Kim L.

1991-01-01

The authors outline the design of an optimal, computationally efficient, infinite impulse response edge detection filter. The optimal filter is computed based on Canny's high signal to noise ratio, good localization criteria, and a criterion on the spurious response of the filter to noise. An expression for the width of the filter, which is appropriate for infinite-length filters, is incorporated directly in the expression for spurious responses. The three criteria are maximized using the variational method and nonlinear constrained optimization. The optimal filter parameters are tabulated for various values of the filter performance criteria. A complete methodology for implementing the optimal filter using approximating recursive digital filtering is presented. The approximating recursive digital filter is separable into two linear filters operating in two orthogonal directions. The implementation is very simple and computationally efficient, has a constant time of execution for different sizes of the operator, and is readily amenable to real-time hardware implementation.

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

Schwartz, C.; Gavin, P.

This report describes research performed at the WSU College of Veterinary Medicine in which a large animal model was developed and used to study the effects of boron neutron capture therapy (BNCT) on normal and neoplastic canine brain tissue. The studies were performed using borocaptate sodium (BSH) and epithermal neutrons and had two major foci: biodistribution of BSH in animals with spontaneously occurring brain tumors; and effects of BNCT in normal and neoplastic brain tissue.

Performance verification of an epithermal neutron flux monitor using accelerator-based BNCT neutron sources

NASA Astrophysics Data System (ADS)

Guan, X.; Murata, I.; Wang, T.

2017-09-01

The performance of an epithermal neutron flux monitor developed for boron neutron capture therapy (BNCT) is verified by Monte Carlo simulations using accelerator-based neutron sources (ABNSs). The results indicate that the developed epithermal neutron flux monitor works well and it can be efficiently used in practical applications to measure the epithermal neutron fluxes of ABNSs in a high accuracy.

Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer.

PubMed

Barth, Rolf F; Vicente, M Graca H; Harling, Otto K; Kiger, W S; Riley, Kent J; Binns, Peter J; Wagner, Franz M; Suzuki, Minoru; Aihara, Teruhito; Kato, Itsuro; Kawabata, Shinji

2012-08-29

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or "BPA", and sodium borocaptate or "BSH" (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.

Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

PubMed Central

2012-01-01

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, the United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options. PMID:22929110

Project for the development of the linac based NCT facility in University of Tsukuba.

PubMed

Kumada, H; Matsumura, A; Sakurai, H; Sakae, T; Yoshioka, M; Kobayashi, H; Matsumoto, H; Kiyanagi, Y; Shibata, T; Nakashima, H

2014-06-01

A project team headed by University of Tsukuba launched the development of a new accelerator based BNCT facility. In the project, we have adopted Radio-Frequency Quadrupole (RFQ)+Drift Tube Linac (DTL) type linac as proton accelerators. Proton energy generated from the linac was set to 8MeV and average current was 10mA. The linac tube has been constructed by Mitsubishi Heavy Industry Co. For neutron generator device, beryllium is selected as neutron target material; high intensity neutrons are generated by the reaction with beryllium and the 80kW proton beam. Our team chose beryllium as the neutron target material. At present beryllium target system is being designed with Monte-Carlo estimations and heat analysis with ANSYS. The neutron generator consists of moderator, collimator and shielding. It is being designed together with the beryllium target system. We also acquired a building in Tokai village; the building has been renovated for use as BNCT treatment facility. It is noteworthy that the linac tube had been installed in the facility in September 2012. In BNCT procedure, several medical devices are required for BNCT treatment such as treatment planning system, patient positioning device and radiation monitors. Thus these are being developed together with the linac based neutron source. For treatment planning system, we are now developing a new multi-modal Monte-Carlo treatment planning system based on JCDS. The system allows us to perform dose estimation for BNCT as well as particle radiotherapy and X-ray therapy. And the patient positioning device can navigate a patient to irradiation position quickly and properly. Furthermore the device is able to monitor movement of the patient׳s position during irradiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2007-10-01

Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria andmore » adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.« less

Present status of Accelerator-Based BNCT.

PubMed

Kreiner, Andres Juan; Bergueiro, Javier; Cartelli, Daniel; Baldo, Matias; Castell, Walter; Asoia, Javier Gomez; Padulo, Javier; Suárez Sandín, Juan Carlos; Igarzabal, Marcelo; Erhardt, Julian; Mercuri, Daniel; Valda, Alejandro A; Minsky, Daniel M; Debray, Mario E; Somacal, Hector R; Capoulat, María Eugenia; Herrera, María S; Del Grosso, Mariela F; Gagetti, Leonardo; Anzorena, Manuel Suarez; Canepa, Nicolas; Real, Nicolas; Gun, Marcelo; Tacca, Hernán

2016-01-01

This work aims at giving an updated report of the worldwide status of Accelerator-Based BNCT (AB-BNCT). There is a generalized perception that the availability of accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of BNCT. Accordingly, in recent years a significant effort has started to develop such machines. A variety of possible charged-particle induced nuclear reactions and the characteristics of the resulting neutron spectra are discussed along with the worldwide activity in suitable accelerator development. Endothermic (7)Li(p,n)(7)Be and (9)Be(p,n)(9)B and exothermic (9)Be(d,n)(10)B are compared. In addition to having much better thermo-mechanical properties than Li, Be as a target leads to stable products. This is a significant advantage for a hospital-based facility. (9)Be(p,n)(9)B needs at least 4-5 MeV bombarding energy to have a sufficient yield, while (9)Be(d,n)(10)B can be utilized at about 1.4 MeV, implying the smallest possible accelerator. This reaction operating with a thin target can produce a sufficiently soft spectrum to be viable for AB-BNCT. The machines considered are electrostatic single ended or tandem accelerators or radiofrequency quadrupoles plus drift tube Linacs. (7)Li(p,n)(7)Be provides one of the best solutions for the production of epithermal neutron beams for deep-seated tumors. However, a Li-based target poses significant technological challenges. Hence, Be has been considered as an alternative target, both in combination with (p,n) and (d,n) reactions. (9)Be(d,n)(10)B at 1.4 MeV, with a thin target has been shown to be a realistic option for the treatment of deep-seated lesions.

MCNP simulation of the dose distribution in liver cancer treatment for BNC therapy

NASA Astrophysics Data System (ADS)

Krstic, Dragana; Jovanovic, Zoran; Markovic, Vladimir; Nikezic, Dragoslav; Urosevic, Vlade

2014-10-01

The Boron Neutron Capture Therapy ( BNCT) is based on selective uptake of boron in tumour tissue compared to the surrounding normal tissue. Infusion of compounds with boron is followed by irradiation with neutrons. Neutron capture on 10B, which gives rise to an alpha particle and recoiled 7Li ion, enables the therapeutic dose to be delivered to tumour tissue while healthy tissue can be spared. Here, therapeutic abilities of BNCT were studied for possible treatment of liver cancer using thermal and epithermal neutron beam. For neutron transport MCNP software was used and doses in organs of interest in ORNL phantom were evaluated. Phantom organs were filled with voxels in order to obtain depth-dose distributions in them. The result suggests that BNCT using an epithermal neutron beam could be applied for liver cancer treatment.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

PubMed

Shu, Di-Yun; Geng, Chang-Ran; Tang, Xiao-Bin; Gong, Chun-Hui; Shao, Wen-Cheng; Ai, Yao

2018-07-01

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT. Copyright © 2018 Elsevier Ltd. All rights reserved.

Application of an octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin (H2OCP) as dual sensitizer for BNCT and PDT

USDA-ARS?s Scientific Manuscript database

The applications of the octa-anionic 5,10,15,20-tetra[3,5-(nidocarboranylmethyl) phenyl]porphyrin (H2OCP) as a boron delivery agent in boron neutron capture therapy (BNCT) and a photosensitizer in photodynamic therapy (PDT) have been investigated. Using F98 Rat glioma cells, we evaluated the cytotox...

Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

NASA Astrophysics Data System (ADS)

Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

2006-03-01

Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours.

PubMed

Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-Ichi; Maruhashi, Akira

2006-03-07

Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system

PubMed Central

NAKAMURA, Satoshi; IMAMICHI, Shoji; MASUMOTO, Kazuyoshi; ITO, Masashi; WAKITA, Akihisa; OKAMOTO, Hiroyuki; NISHIOKA, Shie; IIJIMA, Kotaro; KOBAYASHI, Kazuma; ABE, Yoshihisa; IGAKI, Hiroshi; KURITA, Kazuyoshi; NISHIO, Teiji; MASUTANI, Mitsuko; ITAMI, Jun

2017-01-01

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system. PMID:29225308

Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system.

PubMed

Nakamura, Satoshi; Imamichi, Shoji; Masumoto, Kazuyoshi; Ito, Masashi; Wakita, Akihisa; Okamoto, Hiroyuki; Nishioka, Shie; Iijima, Kotaro; Kobayashi, Kazuma; Abe, Yoshihisa; Igaki, Hiroshi; Kurita, Kazuyoshi; Nishio, Teiji; Masutani, Mitsuko; Itami, Jun

2017-01-01

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24 Na, 38 Cl, 80m Br, 82 Br, 56 Mn, and 42 K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 10 2 , (2.2 ± 0.1) × 10 1 , (3.4 ± 0.4) × 10 2 , 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 10 1 Bq/g/mA, respectively. The 24 Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.

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

Zhai, Ziqing; Kruska, Karen; Toloczko, Mychailo B.

Stress corrosion crack initiation of two thermally-treated, cold-worked (CW) alloy 690 materials was investigated in 360oC simulated PWR primary water using constant load tensile (CLT) tests and blunt notch compact tension (BNCT) tests equipped with direct current potential drop (DCPD) for in-situ detection of cracking. SCC initiation was not detected by DCPD for the 21% and 31%CW CLT specimens loaded at their yield stress after ~9,220 h, however intergranular (IG) precursor damage and isolated surface cracks were observed on the specimens. The two 31%CW BNCT specimens loaded at moderate stress intensity after several cyclic loading ramps showed DCPD-indicated crack initiationmore » after 10,400h exposure at constant stress intensity, which resulted from significant growth of IG cracks. The 21%CW BNCT specimens only exhibited isolated small IG surface cracks and showed no apparent DCPD change throughout the test. Interestingly, post-test cross-section examinations revealed many grain boundary (GB) nano-cavities in the bulk of all the CLT and BNCT specimens particularly for the 31%CW materials. Cavities were also found along GBs extending to the surface suggesting an important role in crack nucleation. This paper provides an overview of the evolution of GB cavities and will discuss their effects on crack initiation in CW alloy 690.« less

GPU-based prompt gamma ray imaging from boron neutron capture therapy.

PubMed

Yoon, Do-Kun; Jung, Joo-Young; Jo Hong, Key; Sil Lee, Keum; Suk Suh, Tae

2015-01-01

The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU). Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations.

L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

PubMed

Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. Copyright © 2015. Published by Elsevier Ireland Ltd.

Development of An Epi-thermal Neutron Field for Fundamental Researches for BNCT with A DT Neutron Source

NASA Astrophysics Data System (ADS)

Osawa, Yuta; Imoto, Shoichi; Kusaka, Sachie; Sato, Fuminobu; Tanoshita, Masahiro; Murata, Isao

2017-09-01

Boron Neutron Capture Therapy (BNCT) is known to be a new promising cancer therapy suppressing influence against normal cells. In Japan, Accelerator Based Neutron Sources (ABNS) are being developed for BNCT. For the spread of ABNS based BNCT, we should characterize the neutron field beforehand. For this purpose, we have been developing a low-energy neutron spectrometer based on 3He position sensitive proportional counter. In this study, a new intense epi-thermal neutron field was developed with a DT neutron source for verification of validity of the spectrometer. After the development, the neutron field characteristics were experimentally evaluated by using activation foils. As a result, we confirmed that an epi-thermal neutron field was successfully developed suppressing fast neutrons substantially. Thereafter, the neutron spectrometer was verified experimentally. In the verification, although a measured detection depth distribution agreed well with the calculated distribution by MCNP, the unfolded spectrum was significantly different from the calculated neutron spectrum due to contribution of the side neutron incidence. Therefore, we designed a new neutron collimator consisting of a polyethylene pre-collimator and boron carbide neutron absorber and confirmed numerically that it could suppress the side incident neutrons and shape the neutron flux to be like a pencil beam.

The effect of spectral filters on visual search in stroke patients.

PubMed

Beasley, Ian G; Davies, Leon N

2013-01-01

Visual search impairment can occur following stroke. The utility of optimal spectral filters on visual search in stroke patients has not been considered to date. The present study measured the effect of optimal spectral filters on visual search response time and accuracy, using a task requiring serial processing. A stroke and control cohort undertook the task three times: (i) using an optimally selected spectral filter; (ii) the subjects were randomly assigned to two groups with group 1 using an optimal filter for two weeks, whereas group 2 used a grey filter for two weeks; (iii) the groups were crossed over with group 1 using a grey filter for a further two weeks and group 2 given an optimal filter, before undertaking the task for the final time. Initial use of an optimal spectral filter improved visual search response time but not error scores in the stroke cohort. Prolonged use of neither an optimal nor a grey filter improved response time or reduced error scores. In fact, response times increased with the filter, regardless of its type, for stroke and control subjects; this outcome may be due to contrast reduction or a reflection of task design, given that significant practice effects were noted.

Development of a new multi-modal Monte-Carlo radiotherapy planning system.

PubMed

Kumada, H; Nakamura, T; Komeda, M; Matsumura, A

2009-07-01

A new multi-modal Monte-Carlo radiotherapy planning system (developing code: JCDS-FX) is under development at Japan Atomic Energy Agency. This system builds on fundamental technologies of JCDS applied to actual boron neutron capture therapy (BNCT) trials in JRR-4. One of features of the JCDS-FX is that PHITS has been applied to particle transport calculation. PHITS is a multi-purpose particle Monte-Carlo transport code. Hence application of PHITS enables to evaluate total doses given to a patient by a combined modality therapy. Moreover, JCDS-FX with PHITS can be used for the study of accelerator based BNCT. To verify calculation accuracy of the JCDS-FX, dose evaluations for neutron irradiation of a cylindrical water phantom and for an actual clinical trial were performed, then the results were compared with calculations by JCDS with MCNP. The verification results demonstrated that JCDS-FX is applicable to BNCT treatment planning in practical use.

Lithium target for accelerator based BNCT neutron source: Influence by the proton irradiation on lithium

NASA Astrophysics Data System (ADS)

Fujii, R.; Imahori, Y.; Nakakmura, M.; Takada, M.; Kamada, S.; Hamano, T.; Hoshi, M.; Sato, H.; Itami, J.; Abe, Y.; Fuse, M.

2012-12-01

The neutron source for Boron Neutron Capture Therapy (BNCT) is in the transition stage from nuclear reactor to accelerator based neutron source. Generation of low energy neutron can be achieved by 7Li (p, n) 7Be reaction using accelerator based neutron source. Development of small-scale and safe neutron source is within reach. The melting point of lithium that is used for the target is low, and durability is questioned for an extended use at a high current proton beam. In order to test its durability, we have irradiated lithium with proton beam at the same level as the actual current density, and found no deterioration after 3 hours of continuous irradiation. As a result, it is suggested that lithium target can withstand proton irradiation at high current, confirming suitability as accelerator based neutron source for BNCT.

MCNP study for epithermal neutron irradiation of an isolated liver at the Finnish BNCT facility.

PubMed

Kotiluoto, P; Auterinen, I

2004-11-01

A successful boron neutron capture treatment (BNCT) of a patient with multiple liver metastases has been first given in Italy, by placing the removed organ into the thermal neutron column of the Triga research reactor of the University of Pavia. In Finland, FiR 1 Triga reactor with an epithermal neutron beam well suited for BNCT has been extensively used to irradiate patients with brain tumors such as glioblastoma and recently also head and neck tumors. In this work we have studied by MCNP Monte Carlo simulations, whether it would be beneficial to treat an isolated liver with epithermal neutrons instead of thermal ones. The results show, that the epithermal field penetrates deeper into the liver and creates a build-up distribution of the boron dose. Our results strongly encourage further studying of irradiation arrangement of an isolated liver with epithermal neutron fields.

Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation.

PubMed

Zaboronok, A; Yamamoto, T; Nakai, K; Yoshida, F; Uspenskii, S; Selyanin, M; Zelenetskii, A; Matsumura, Akira

2015-12-01

Hyaluronic acid (HA), a nonimmunogenic, biocompatible polymer found in different biological tissues, has the potential to attach to CD44 receptors on the surface of certain cancer cells, where the receptor is overexpressed compared with normal cells. Boron-hyaluronic acid (BHA) was tested for its feasibility as a potential agent for BNCT. BHA with low-viscosity 30 kDa HA could be administered by intravenous injection. The compound showed a certain degree of cytotoxicity and accumulation in C6 rat glioma cells in vitro. Instability of the chelate bonds between boron and HA and/or insufficient specificity of CD44 receptors on C6 cells to BHA could account for the insufficient in vitro accumulation. To ensure the future eligibility of BHA for BNCT experiments, using alternative tumor cell lines and chemically securing the chelate bonds or synthesizing BHA with boron covalently attached to HA might be required. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility of sealed D-T neutron generator as neutron source for liver BNCT and its beam shaping assembly.

PubMed

Liu, Zheng; Li, Gang; Liu, Linmao

2014-04-01

This paper involves the feasibility of boron neutron capture therapy (BNCT) for liver tumor with four sealed neutron generators as neutron source. Two generators are placed on each side of the liver. The high energy of these emitted neutrons should be reduced by designing a beam shaping assembly (BSA) to make them useable for BNCT. However, the neutron flux decreases as neutrons pass through different materials of BSA. Therefore, it is essential to find ways to increase the neutron flux. In this paper, the feasibility of using low enrichment uranium as a neutron multiplier is investigated to increase the number of neutrons emitted from D-T neutron generators. The neutron spectrum related to our system has a proper epithermal flux, and the fast and thermal neutron fluxes comply with the IAEA recommended values. Copyright © 2014 Elsevier Ltd. All rights reserved.

SU-E-J-100: Reconstruction of Prompt Gamma Ray Three Dimensional SPECT Image From Boron Neutron Capture Therapy(BNCT)

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

Yoon, D; Jung, J; Suh, T

2014-06-01

Purpose: Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography (SPECT) image from boron neutron capture therapy (BNCT) using Monte Carlo simulation. Methods: In case of simulation, the pixelated SPECT detector, collimator and phantom were simulated using Monte Carlo n particle extended (MCNPX) simulation tool. A thermal neutron source (<1 eV) was used to react with the boron uptake region (BUR) in the phantom. Each geometry had a spherical pattern, and three different BURs (A, B and C region, density: 2.08 g/cm3) were located in the middle of the brain phantom.more » The data from 128 projections for each sorting process were used to achieve image reconstruction. The ordered subset expectation maximization (OSEM) reconstruction algorithm was used to obtain a tomographic image with eight subsets and five iterations. The receiver operating characteristic (ROC) curve analysis was used to evaluate the geometric accuracy of reconstructed image. Results: The OSEM image was compared with the original phantom pattern image. The area under the curve (AUC) was calculated as the gross area under each ROC curve. The three calculated AUC values were 0.738 (A region), 0.623 (B region), and 0.817 (C region). The differences between length of centers of two boron regions and distance of maximum count points were 0.3 cm, 1.6 cm and 1.4 cm. Conclusion: The possibility of extracting a 3D BNCT SPECT image was confirmed using the Monte Carlo simulation and OSEM algorithm. The prospects for obtaining an actual BNCT SPECT image were estimated from the quality of the simulated image and the simulation conditions. When multiple tumor region should be treated using the BNCT, a reasonable model to determine how many useful images can be obtained from the SPECT could be provided to the BNCT facilities. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (MSIP)(Grant No.200900420) and the Radiation Technology Research and Development program (Grant No.2013043498), Republic of Korea.« less

Prompt gamma and neutron detection in BNCT utilizing a CdTe detector.

PubMed

Winkler, Alexander; Koivunoro, Hanna; Reijonen, Vappu; Auterinen, Iiro; Savolainen, Sauli

2015-12-01

In this work, a novel sensor technology based on CdTe detectors was tested for prompt gamma and neutron detection using boronated targets in (epi)thermal neutron beam at FiR1 research reactor in Espoo, Finland. Dedicated neutron filter structures were omitted to enable simultaneous measurement of both gamma and neutron radiation at low reactor power (2.5 kW). Spectra were collected and analyzed in four different setups in order to study the feasibility of the detector to measure 478 keV prompt gamma photons released from the neutron capture reaction of boron-10. The detector proved to have the required sensitivity to detect and separate the signals from both boron neutron and cadmium neutron capture reactions, which makes it a promising candidate for monitoring the spatial and temporal development of in vivo boron distribution in boron neutron capture therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model

PubMed Central

Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

2015-01-01

Abstract The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and 7Li particles from the 10B(n, α)7Li reaction, 0.54-MeV protons from the 14N(n, p)14C reaction, the recoiled protons from the 1H(n, n) 1H reaction, and photons from the neutron beam and 1H(n, γ)2H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT. PMID:25428243

The Perspectives of the Boron Neutron Capture Therapy-Clinical Applications Research and Development in Saudi Arabia

NASA Astrophysics Data System (ADS)

Badhrees, I.; Alrumayan, F.; Mahube, F.

Boron Neutron Capture Therapy (BNCT) is a binary form of experimental radiotherapy which is based on the administration of a drug able to concentrate the isotopes in a tumor cell that later are irradiated with a neutron beam. Even though the first evidence of the success of this treatment dates back many years ago, BNCT showed successful treatment results in malignant melanoma, and Glioblastoma. In order for BNCT to be successful, a sufficient amount of Boron (10B) must be selectively delivered to the tumor cell, and then irradiated by neutrons of sufficient enough. The CS-30 cyclotron at King Faisal Specialist Hospital & Research Center is a positive-ion machine capable of accelerating protons at 26MeV, and other isotopes as well. Although the peak beam intensity from the CS-30 is low, the key to success of using it for the BNCT is by using a high average beam current at low energy. This work is aimed at testing the capability of the CS-30 Cyclotron to produce a low-energy neutron beam to be used to activate the Boron atoms injected into the tumor cell, through simulation of a compatible moderator. We are also planning to measure the overall dosimetry of the energy dose as well as that for the boron in the tumor cell.

Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

PubMed

Halfon, S; Arenshtam, A; Kijel, D; Paul, M; Weissman, L; Berkovits, D; Eliyahu, I; Feinberg, G; Kreisel, A; Mardor, I; Shimel, G; Shor, A; Silverman, I; Tessler, M

2015-12-01

A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Precursor Evolution and Stress Corrosion Cracking Initiation of Cold-Worked Alloy 690 in Simulated Pressurized Water Reactor Primary Water

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

Zhai, Ziqing; Toloczko, Mychailo; Kruska, Karen

Stress corrosion crack initiation of two thermally-treated, cold-worked (CW) alloy 690 (UNS N06690) materials was investigated in 360oC simulated PWR primary water using constant load tensile (CLT) tests and blunt notch compact tension (BNCT) tests equipped with direct current potential drop (DCPD) for in-situ detection of cracking. SCC initiation was not detected by DCPD for either the 21% or 31%CW CLT specimens loaded at their yield stress after ~9,220 hours, however intergranular (IG) precursor damage and isolated surface cracks were observed on the specimens. The two 31%CW BNCT specimens loaded at moderate stress intensity after several cyclic loading ramps showedmore » DCPD-indicated crack initiation after 10,400 hours of exposure at constant stress intensity, which was resulted from significant growth of IG cracks. The 21%CW BNCT specimens only exhibited isolated small IG surface cracks and showed no apparent DCPD change throughout the test. Post-test cross-section examinations revealed many grain boundary (GB) nano-cavities in the bulk of all the CLT and BNCT specimens particularly for the 31%CW materials. Cavities were also found along GBs extending to the surface suggesting an important role in crack nucleation. This paper provides an overview of the evolution of GB cavities and discusses their effects on crack initiation in CW alloy 690.« less

GPU-based prompt gamma ray imaging from boron neutron capture therapy

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

Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae, E-mail: suhsanta@catholic.ac.kr

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU).more » Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusions: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations.« less

TU-FG-BRB-07: GPU-Based Prompt Gamma Ray Imaging From Boron Neutron Capture Therapy

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

Kim, S; Suh, T; Yoon, D

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU).more » Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusion: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray reconstruction using the GPU computation for BNCT simulations.« less

Inverse design of high-Q wave filters in two-dimensional phononic crystals by topology optimization.

PubMed

Dong, Hao-Wen; Wang, Yue-Sheng; Zhang, Chuanzeng

2017-04-01

Topology optimization of a waveguide-cavity structure in phononic crystals for designing narrow band filters under the given operating frequencies is presented in this paper. We show that it is possible to obtain an ultra-high-Q filter by only optimizing the cavity topology without introducing any other coupling medium. The optimized cavity with highly symmetric resonance can be utilized as the multi-channel filter, raising filter and T-splitter. In addition, most optimized high-Q filters have the Fano resonances near the resonant frequencies. Furthermore, our filter optimization based on the waveguide and cavity, and our simple illustration of a computational approach to wave control in phononic crystals can be extended and applied to design other acoustic devices or even opto-mechanical devices. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

PubMed Central

Barth, Rolf F.; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji

2017-01-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event. PMID:28534152

Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

PubMed

Perona, M; Rodríguez, C; Carpano, M; Thomasz, L; Nievas, S; Olivera, M; Thorp, S; Curotto, P; Pozzi, E; Kahl, S; Pisarev, M; Juvenal, G; Dagrosa, A

2013-08-01

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹⁰BPA (10 μg ¹⁰B ml⁻¹) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ¹⁰BOPP (10 μg ¹⁰B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹⁰ n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma.

PubMed

Kondo, Natsuko; Barth, Rolf F; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji; Lehman, Norman L

2017-05-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1 R132H , were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1 R132H -positive and 1 control IDH1 R132H -negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1 R132H -negative small cell GBMs. The remaining patients had tumors consisting of other IDH1 R132H -negative GBM variants, an IDH1 R132H -positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1 R132H -negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

Dose-rate effect was observed in T98G glioma cells following BNCT.

PubMed

Kinashi, Yuko; Okumura, Kakuji; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

2014-06-01

It is generally said that low LET radiation produce high dose-rate effect, on the other hand, no significant dose rate effect is observed in high LET radiation. Although high LET radiations are produced in BNCT, little is known about dose-rate effect of BNCT. T98G cells, which were tumor cells, were irradiated by neutron mixed beam with BPA. As normal tissue derived cells, Chinese hamster ovary (CHO-K1) cells and DNA double strand breaks (DNA-DSBs) repair deficient cells, xrs5 cells were irradiated by the neutrons (not including BPA). To DNA-DSBs analysis, T98G cells were stained immunochemically with 53BP1 antibody. The number of DNA-DSBs was determined by counting 53BP1 foci. There was no dose-rate effect in xrs5 cells. D0 difference between 4cGy/min and 20cGy/min irradiation were 0.5 and 5.9 at the neutron and gamma-ray irradiation for CHO-K1, and 0.3 at the neutron for T98G cells. D0 difference between 20cGy/min and 80cGy/min irradiation for T98G cells were 1.2 and 0.6 at neutron irradiation plus BPA and gamma-ray. The differences between neutron irradiations at the dose rate in T98G cells were supported by not only the cell viability but also 53BP1 foci assay at 24h following irradiation to monitor DNA-DSBs. Dose-rate effect of BNCT when T98G cells include 20ppm BPA was greater than that of gamma-ray irradiation. Moreover, Dose-rate effect of the neutron beam when CHO-K1 cells did not include BPA was less than that of gamma-ray irradiation These present results may suggest the importance of dose-rate effect for more efficient BNCT and the side effect reduction. © 2013 Published by Elsevier Ltd.

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions.

PubMed

Ishikawa, Masayori; Yamamoto, Tetsuya; Matsumura, Akira; Hiratsuka, Junichi; Miyatake, Shin-Ichi; Kato, Itsuro; Sakurai, Yoshinori; Kumada, Hiroaki; Shrestha, Shubhechha J; Ono, Koji

2016-08-09

Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

Present status of Accelerator-Based BNCT

PubMed Central

Kreiner, Andres Juan; Bergueiro, Javier; Cartelli, Daniel; Baldo, Matias; Castell, Walter; Asoia, Javier Gomez; Padulo, Javier; Suárez Sandín, Juan Carlos; Igarzabal, Marcelo; Erhardt, Julian; Mercuri, Daniel; Valda, Alejandro A.; Minsky, Daniel M.; Debray, Mario E.; Somacal, Hector R.; Capoulat, María Eugenia; Herrera, María S.; del Grosso, Mariela F.; Gagetti, Leonardo; Anzorena, Manuel Suarez; Canepa, Nicolas; Real, Nicolas; Gun, Marcelo; Tacca, Hernán

2016-01-01

Aim This work aims at giving an updated report of the worldwide status of Accelerator-Based BNCT (AB-BNCT). Background There is a generalized perception that the availability of accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of BNCT. Accordingly, in recent years a significant effort has started to develop such machines. Materials and methods A variety of possible charged-particle induced nuclear reactions and the characteristics of the resulting neutron spectra are discussed along with the worldwide activity in suitable accelerator development. Results Endothermic 7Li(p,n)7Be and 9Be(p,n)9B and exothermic 9Be(d,n)10B are compared. In addition to having much better thermo-mechanical properties than Li, Be as a target leads to stable products. This is a significant advantage for a hospital-based facility. 9Be(p,n)9B needs at least 4–5 MeV bombarding energy to have a sufficient yield, while 9Be(d,n)10B can be utilized at about 1.4 MeV, implying the smallest possible accelerator. This reaction operating with a thin target can produce a sufficiently soft spectrum to be viable for AB-BNCT. The machines considered are electrostatic single ended or tandem accelerators or radiofrequency quadrupoles plus drift tube Linacs. Conclusions 7Li(p,n)7Be provides one of the best solutions for the production of epithermal neutron beams for deep-seated tumors. However, a Li-based target poses significant technological challenges. Hence, Be has been considered as an alternative target, both in combination with (p,n) and (d,n) reactions. 9Be(d,n)10B at 1.4 MeV, with a thin target has been shown to be a realistic option for the treatment of deep-seated lesions. PMID:26933390

Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors.

PubMed

Blue, Thomas E; Yanch, Jacquelyn C

2003-01-01

This paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (approximately 1.5 M dollars) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (approximately 10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and the use of microchannels have emerged as viable target cooling options. Neutron fields for reactor-based neutron sources provide an obvious basis of comparison for ABNS field quality. This paper compares Monte Carlo calculations of neutron field quality for an ABNS and an idealized standard reactor neutron field (ISRNF). The comparison shows that with lithium as a target, an ABNS can create a neutron field with a field quality that is significantly better (by a factor of approximately 1.2, as judged by the relative biological effectiveness (RBE)-dose that can be delivered to a tumor at a depth of 6cm) than that for the ISRNF. Also, for a beam current of 10 mA, the treatment time is calculated to be reasonable (approximately 30 min) for the boron concentrations that have been assumed.

124Sb-Be photo-neutron source for BNCT: Is it possible?

NASA Astrophysics Data System (ADS)

Golshanian, Mohadeseh; Rajabi, Ali Akbar; Kasesaz, Yaser

2016-11-01

In this research a computational feasibility study has been done on the use of 124SbBe photo-neutron source for Boron Neutron Capture Therapy (BNCT) using MCNPX Monte Carlo code. For this purpose, a special beam shaping assembly has been designed to provide an appropriate epithermal neutron beam suitable for BNCT. The final result shows that using 150 kCi of 124Sb, the epithermal neutron flux at the designed beam exit is 0.23×109 (n/cm2 s). In-phantom dose analysis indicates that treatment time for a brain tumor is about 40 min which is a reasonable time. This high activity 124Sb could be achieved using three 50 kCi rods of 124Sb which can be produced in a research reactor. It is clear, that as this activity is several hundred times the activity of a typical cobalt radiotherapy source, issues related to handling, safety and security must be addressed.

Shielding analyses of an AB-BNCT facility using Monte Carlo simulations and simplified methods

NASA Astrophysics Data System (ADS)

Lai, Bo-Lun; Sheu, Rong-Jiun

2017-09-01

Accurate Monte Carlo simulations and simplified methods were used to investigate the shielding requirements of a hypothetical accelerator-based boron neutron capture therapy (AB-BNCT) facility that included an accelerator room and a patient treatment room. The epithermal neutron beam for BNCT purpose was generated by coupling a neutron production target with a specially designed beam shaping assembly (BSA), which was embedded in the partition wall between the two rooms. Neutrons were produced from a beryllium target bombarded by 1-mA 30-MeV protons. The MCNP6-generated surface sources around all the exterior surfaces of the BSA were established to facilitate repeated Monte Carlo shielding calculations. In addition, three simplified models based on a point-source line-of-sight approximation were developed and their predictions were compared with the reference Monte Carlo results. The comparison determined which model resulted in better dose estimation, forming the basis of future design activities for the first ABBNCT facility in Taiwan.

Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Corti, M.; Bonora, M.; Borsa, F.; Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S.; Zonta, C.; Clerici, A. M.; Cansolino, L.; Ferrari, C.; Dionigi, P.; Porta, A.; Zanoni, G.; Vidari, G.

2011-04-01

We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of 10B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by α spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R1 between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

An accelerator-based Boron Neutron Capture Therapy (BNCT) facility based on the 7Li(p,n)7Be

NASA Astrophysics Data System (ADS)

Musacchio González, Elizabeth; Martín Hernández, Guido

2017-09-01

BNCT (Boron Neutron Capture Therapy) is a therapeutic modality used to irradiate tumors cells previously loaded with the stable isotope 10B, with thermal or epithermal neutrons. This technique is capable of delivering a high dose to the tumor cells while the healthy surrounding tissue receive a much lower dose depending on the 10B biodistribution. In this study, therapeutic gain and tumor dose per target power, as parameters to evaluate the treatment quality, were calculated. The common neutron-producing reaction 7Li(p,n)7Be for accelerator-based BNCT, having a reaction threshold of 1880.4 keV, was considered as the primary source of neutrons. Energies near the reaction threshold for deep-seated brain tumors were employed. These calculations were performed with the Monte Carlo N-Particle (MCNP) code. A simple but effective beam shaping assembly (BSA) was calculated producing a high therapeutic gain compared to previously proposed facilities with the same nuclear reaction.

Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines.

PubMed

Rossini, Andrés E; Dagrosa, Maria A; Portu, Agustina; Saint Martin, Giselle; Thorp, Silvia; Casal, Mariana; Navarro, Aimé; Juvenal, Guillermo J; Pisarev, Mario A

2015-01-01

In order to optimize the effectiveness of Boron Neutron Capture Therapy (BNCT), Relative Biological Effectiveness (RBE) and Compound Biological Effectiveness (CBE) were determined in two human melanoma cell lines, M8 and Mel-J cells, using the amino acid p-boronophenylalanine (BPA) as boron carrier. The effects of BNCT on the primary amelanotic cell line M8 and on the metastatic pigmented melanoma cell line Mel-J were studied using colony formation assay. The RBE values were determined using both a gamma ray source, and the neutron beam from the Nuclear Reactor of the National Atomic Energy Commission (RA-3). For the determination of the RBE, cells were irradiated with increasing doses of both sources, between 1 and 8 Gy; and for the determination of CBE factors, the cells were pre-incubated with BPA before irradiation. Afterwards, the cell surviving fraction (SF) was determined for each treatment. Marked differences were observed between both cell lines. Mel-J cells were more radioresistant than the M8 cell line. The clonogenic assays showed that for a SF of 1%, the RBE values were 1.3 for M8 cells and 1.5 for Mel-J cells. Similarly, the CBE values for a 1% SF were 2.1 for M8 and 3 for Mel-J cell lines. For the endpoint of 0.1% of SF the RBE values obtained were 1.2 for M8 and 1.4 for Mel-J cells. Finally, CBE values calculated for a 0.1% were 2 and 2.6 for M8 and Mel-J cell lines respectively. In order to estimate the uptake of the non-radioactive isotope Boron 10 ((10)B), a neutron induced autoradiographic technique was performed showing discrepancies in (10)B uptake between both cell lines. These obtained in vitro results are the first effectiveness factors determined for human melanoma at the RA-3 nuclear reactor and show that BNCT dosimetry planning for patients could be successfully performed using these new factors.

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

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model.

PubMed

Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

2015-03-01

The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and (7)Li particles from the (10)B(n, α)(7)Li reaction, 0.54-MeV protons from the (14)N(n, p)(14)C reaction, the recoiled protons from the (1)H(n, n) (1)H reaction, and photons from the neutron beam and (1)H(n, γ)(2)H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Thermal neutron flux mapping in a head phantom

NASA Astrophysics Data System (ADS)

Lee, C. L.; Zhou, X.-L.; Harmon, J. F.; Bartholomay, R. W.; Harker, Y. D.; Kudchadker, R. J.

1999-02-01

Boron neutron capture therapy (BNCT) is a binary cancer treatment modality in which a boron-containing compound is preferentially loaded into a tumor, followed by irradiation by thermal neutrons. In accelerator-based BNCT, neutrons are produced by charged particle-induced reactions such as 7Li(p, n) 7Be. For deeply seated brain tumors, epithermal (1 eV to 10 kev) neutrons are needed to penetrate the skull cap and subsequently thermalize at the tumor location. Cell damage in BNCT is caused by the high linear energy transfer (LET) products from the 10B(n, α) 7Li reaction. Because the cross section for this reaction is of 1/ v character, the dose due to 10B has essentially the same spatial distribution as the thermal neutron flux. A cylindrical acrylic head phantom (15.24 cm diameter by 21.59 cm length) has been constructed to simulate the patient's head and neck, and acrylic spacers of varying width allow placement of small (active sizes: 0.635 cm diameter by 1.27 cm length and 1.5875 cm diameter by 2.54 cm length) BF 3 proportional counters at nearly all radial and axial locations. Measurements of the thermal flux have also been benchmarked with gold and indium foils (bare and cadmium covered), as well as MCNP simulations. Measurement of the thermal neutron flux using these small BF 3 counters is shown to be adequate for experimentally determining the spatial variation of the 10B dose in head phantoms for accelerator-based BNCT.

Method for optimizing output in ultrashort-pulse multipass laser amplifiers with selective use of a spectral filter

DOEpatents

Backus, Sterling J [Erie, CO; Kapteyn, Henry C [Boulder, CO

2007-07-10

A method for optimizing multipass laser amplifier output utilizes a spectral filter in early passes but not in later passes. The pulses shift position slightly for each pass through the amplifier, and the filter is placed such that early passes intersect the filter while later passes bypass it. The filter position may be adjust offline in order to adjust the number of passes in each category. The filter may be optimized for use in a cryogenic amplifier.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

NASA Astrophysics Data System (ADS)

González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

2017-10-01

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

PubMed

González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

2017-10-03

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Bayesian Regression with Network Prior: Optimal Bayesian Filtering Perspective

PubMed Central

Qian, Xiaoning; Dougherty, Edward R.

2017-01-01

The recently introduced intrinsically Bayesian robust filter (IBRF) provides fully optimal filtering relative to a prior distribution over an uncertainty class ofjoint random process models, whereas formerly the theory was limited to model-constrained Bayesian robust filters, for which optimization was limited to the filters that are optimal for models in the uncertainty class. This paper extends the IBRF theory to the situation where there are both a prior on the uncertainty class and sample data. The result is optimal Bayesian filtering (OBF), where optimality is relative to the posterior distribution derived from the prior and the data. The IBRF theories for effective characteristics and canonical expansions extend to the OBF setting. A salient focus of the present work is to demonstrate the advantages of Bayesian regression within the OBF setting over the classical Bayesian approach in the context otlinear Gaussian models. PMID:28824268

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy

PubMed Central

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-01-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their 24Na and 38Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to 24Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive 24Na is mainly generated from 23Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood 24Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood 24Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood 24Na was determined using a germanium counter. The activity of 24Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood 24Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible. PMID:23392825

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy.

PubMed

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-07-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their (24)Na and (38)Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to (24)Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive (24)Na is mainly generated from (23)Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood (24)Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood (24)Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood (24)Na was determined using a germanium counter. The activity of (24)Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood (24)Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible.

Characterisation of an accelerator-based neutron source for BNCT versus beam energy

NASA Astrophysics Data System (ADS)

Agosteo, S.; Curzio, G.; d'Errico, F.; Nath, R.; Tinti, R.

2002-01-01

Neutron capture in 10B produces energetic alpha particles that have a high linear energy transfer in tissue. This results in higher cell killing and a higher relative biological effectiveness compared to photons. Using suitably designed boron compounds which preferentially localize in cancerous cells instead of healthy tissues, boron neutron capture therapy (BNCT) has the potential of providing a higher tumor cure rate within minimal toxicity to normal tissues. This clinical approach requires a thermal neutron source, generally a nuclear reactor, with a fluence rate sufficient to deliver tumorcidal doses within a reasonable treatment time (minutes). Thermal neutrons do not penetrate deeply in tissue, therefore BNCT is limited to lesions which are either superficial or otherwise accessible. In this work, we investigate the feasibility of an accelerator-based thermal neutron source for the BNCT of skin melanomas. The source was designed via MCNP Monte Carlo simulations of the thermalization of a fast neutron beam, generated by 7 MeV deuterons impinging on a thick target of beryllium. The neutron field was characterized at several deuteron energies (3.0-6.5 MeV) in an experimental structure installed at the Van De Graaff accelerator of the Laboratori Nazionali di Legnaro, in Italy. Thermal and epithermal neutron fluences were measured with activation techniques and fast neutron spectra were determined with superheated drop detectors (SDD). These neutron spectrometry and dosimetry studies indicated that the fast neutron dose is unacceptably high in the current design. Modifications to the current design to overcome this problem are presented.

Optimization of OT-MACH Filter Generation for Target Recognition

NASA Technical Reports Server (NTRS)

Johnson, Oliver C.; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

2009-01-01

An automatic Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter generator for use in a gray-scale optical correlator (GOC) has been developed for improved target detection at JPL. While the OT-MACH filter has been shown to be an optimal filter for target detection, actually solving for the optimum is too computationally intensive for multiple targets. Instead, an adaptive step gradient descent method was tested to iteratively optimize the three OT-MACH parameters, alpha, beta, and gamma. The feedback for the gradient descent method was a composite of the performance measures, correlation peak height and peak to side lobe ratio. The automated method generated and tested multiple filters in order to approach the optimal filter quicker and more reliably than the current manual method. Initial usage and testing has shown preliminary success at finding an approximation of the optimal filter, in terms of alpha, beta, gamma values. This corresponded to a substantial improvement in detection performance where the true positive rate increased for the same average false positives per image.

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

PubMed

Seki, Keiko; Kinashi, Yuko; Takahashi, Sentaro

2015-01-01

The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The accelerator neutron source for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Kasatov, D.; Koshkarev, A.; Kuznetsov, A.; Makarov, A.; Ostreinov, Yu; Shchudlo, I.; Sorokin, I.; Sycheva, T.; Taskaev, S.; Zaidi, L.

2016-11-01

The accelerator based epithermal neutron source for Boron Neutron Capture Therapy (BNCT) is proposed, created and used in the Budker Institute of Nuclear Physics. In 2014, with the support of the Russian Science Foundation created the BNCT laboratory for the purpose to the end of 2016 get the neutron flux, suitable for BNCT. For getting 3 mA 2.3 MeV proton beam, was created a new type accelerator - tandem accelerator with vacuum isolation. On this moment, we have a stationary proton beam with 2.3 MeV and current 1.75 mA. Generation of neutrons is carried out by dropping proton beam on to lithium target as a result of threshold reaction 7Li(p,n)7Be. Established facility is a unique scientific installation. It provides a generating of neutron flux, including a monochromatic energy neutrons, gamma radiation, alpha-particles and positrons, and may be used by other research groups for carrying out scientific researches. The article describes an accelerator neutron source, presents and discusses the result of experiments and declares future plans.

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy

PubMed Central

Heikkinen, Sami; Kotiluoto, Petri; Serén, Tom; Seppälä, Tiina; Auterinen, Iiro; Savolainen, Sauli

2007-01-01

Radiation‐sensitive polymer gels are among the most promising three‐dimensional dose verification tools developed to date. We tested the normoxic polymer gel dosimeter known by the acronym MAGIC (methacrylic and ascorbic acid in gelatin initiated by copper) to evaluate its use in boron neutron capture therapy (BNCT) dosimetry. We irradiated a large cylindrical gel phantom (diameter: 10 cm; length: 20 cm) in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. To compare dose–response, gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator. Irradiated gel phantoms then underwent magnetic resonance imaging to determine their R2 relaxation rate maps. The measured and normalized dose distribution in the epithermal neutron beam was compared with the dose distribution calculated by computer simulation. The results support the feasibility of using MAGIC gel in BNCT dosimetry. PACS numbers: 87.53.Qc, 87.53.Wz, 87.66.Ff PMID:17592463

Feasibility of the Utilization of BNCT in the Fast Neutron Therapy Beam at Fermilab

DOE R&D Accomplishments Database

Langen, Katja; Lennox, Arlene J.; Kroc, Thomas K.; DeLuca, Jr., Paul M.

2000-06-01

The Neutron Therapy Facility at Fermilab has treated cancer patients since 1976. Since then more than 2,300 patients have been treated and a wealth of clinical information accumulated. The therapeutic neutron beam at Fermilab is produced by bombarding a beryllium target with 66 MeV protons. The resulting continuous neutron spectrum ranges from thermal to 66 MeV in neutron energy. It is clear that this spectrum is not well suited for the treatment of tumors with boron neutron capture therapy (BNCT) only However, since this spectrum contains thermal and epithermal components the authors are investigating whether BNCT can be used in this beam to boost the tumor dose. There are clinical scenarios in which a selective tumor dose boost of 10 - 15% could be clinically significant. For these cases the principal treatment would still be fast neutron therapy but a tumor boost could be used either to deliver a higher dose to the tumor tissue or to reduce the dose to the normal healthy tissue while maintaining the absorbed dose level in the tumor tissue.

Are high energy proton beams ideal for AB-BNCT? A brief discussion from the viewpoint of fast neutron contamination control.

PubMed

Lee, Pei-Yi; Liu, Yuan-Hao; Jiang, Shiang-Huei

2014-06-01

High energy proton beam (>8MeV) is favorable for producing neutrons with high yield. However, the produced neutrons are of high energies. These high energy neutrons can cause severe fast neutron contamination and degrade the BNCT treatment quality if they are not appropriately moderated. Hence, this study aims to briefly discuss the issue, from the viewpoint of fast neutron contamination control, whether high energy proton beam is ideal for AB-BNCT or not. In this study, D2O, PbF4, CaF2, and Fluental(™) were used standalone as moderator materials to slow down 1-, 6-, and 10-MeV parallelly incident neutrons. From the calculated results, we concluded that neutrons produced by high energy proton beam could not be easily moderated by a single moderator to an acceptable contamination level and still with reasonable epithermal neutron beam intensity. Hence, much more complicated and sophisticated designs of beam shaping assembly have to be developed when using high energy proton beams. Copyright © 2014 Elsevier Ltd. All rights reserved.

Teaching-learning-based Optimization Algorithm for Parameter Identification in the Design of IIR Filters

NASA Astrophysics Data System (ADS)

Singh, R.; Verma, H. K.

2013-12-01

This paper presents a teaching-learning-based optimization (TLBO) algorithm to solve parameter identification problems in the designing of digital infinite impulse response (IIR) filter. TLBO based filter modelling is applied to calculate the parameters of unknown plant in simulations. Unlike other heuristic search algorithms, TLBO algorithm is an algorithm-specific parameter-less algorithm. In this paper big bang-big crunch (BB-BC) optimization and PSO algorithms are also applied to filter design for comparison. Unknown filter parameters are considered as a vector to be optimized by these algorithms. MATLAB programming is used for implementation of proposed algorithms. Experimental results show that the TLBO is more accurate to estimate the filter parameters than the BB-BC optimization algorithm and has faster convergence rate when compared to PSO algorithm. TLBO is used where accuracy is more essential than the convergence speed.

Optimization of In-Cylinder Pressure Filter for Engine Research

DTIC Science & Technology

2017-06-01

ARL-TR-8034 ● JUN 2017 US Army Research Laboratory Optimization of In-Cylinder Pressure Filter for Engine Research by Kenneth...Laboratory Optimization of In-Cylinder Pressure Filter for Engine Research by Kenneth S Kim, Michael T Szedlmayer, Kurt M Kruger, and Chol-Bum M...

Multipurpose epithermal neutron beam on new research station at MARIA research reactor in Swierk-Poland

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

Gryzinski, M.A.; Maciak, M.

MARIA reactor is an open-pool research reactor what gives the chance to install uranium fission converter on the periphery of the core. It could be installed far enough not to induce reactivity of the core but close enough to produce high flux of fast neutrons. Special design of the converter is now under construction. It is planned to set the research stand based on such uranium converter in the near future: in 2015 MARIA reactor infrastructure should be ready (preparation started in 2013), in 2016 the neutron beam starts and in 2017 opening the stand for material and biological researchmore » or for medical training concerning BNCT. Unused for many years, horizontal channel number H2 at MARIA research rector in Poland, is going to be prepared as a part of unique stand. The characteristics of the neutron beam will be significant advantage of the facility. High flux of neutrons at the level of 2x10{sup 9} cm{sup -2}s{sup -1} will be obtainable by uranium neutron converter located 90 cm far from the reactor core fuel elements (still inside reactor core basket between so called core reflectors). Due to reaction of core neutrons with converter U{sub 3}Si{sub 2} material it will produce high flux of fast neutrons. After conversion neutrons will be collimated and moderated in the channel by special set of filters and moderators. At the end of H2 channel i.e. at the entrance to the research room neutron energy will be in the epithermal energy range with neutron intensity at least at the level required for BNCT (2x10{sup 9} cm{sup -2}s{sup -1}). For other purposes density of the neutron flux could be smaller. The possibility to change type and amount of installed filters/moderators which enables getting different properties of the beam (neutron energy spectrum, neutron-gamma ratio and beam profile and shape) is taken into account. H2 channel is located in separate room which is adjacent to two other empty rooms under the preparation for research laboratories (200 m2). It is planned to create fully equipped complex facility possible to perform various experiments on the intensive neutron beam. Epithermal neutron beam enables development across the full spectrum of materials research for example shielding concrete tests or electronic devices construction improvement. Due to recent reports on the construction of the accelerator for the Boron Neutron Capture Therapy (BNCT) it has the opportunity to become useful and successful method in the fight against brain and other types of cancers not treated with well known medical methods. In Europe there is no such epithermal neutron source which could be used throughout the year for training and research for scientist working on BNCT what makes the stand unique in Europe. Also our research group which specializes in mixed radiation dosimetry around nuclear and medical facilities would be able to carry out research on new detectors and methods of measurements for radiological protection and in-beam (therapeutic) dosimetry. Another group of scientists from National Centre for Nuclear Research, where MARIA research reactor is located, is involved in research of gamma detector systems. There is an idea to develop Prompt-gamma Single Photon Emission Computed Tomography (Pg- SPECT). This method could be used as imaging system for compounds emitting gamma rays after nuclear reaction with thermal neutrons e.g. for boron concentration in BNCT. Inside the room, where H2 channel is located, there is another horizontal channel - H1 which is also unused. Simultaneously with the construction of the H2 stand it will be possible to create special pneumatic horizontal mail inside the H1 channel for irradiation material samples in the vicinity of the core i.e. in the distal part of the H1 channel. It might expand the scope of research at the planned neutron station. Secondly it is planned to equip both stands with moveable positioning system, video system and facilities to perform animal experiments (anaesthesia, vital signs control, imaging devices, positioning). These all above make constructed station unique in the world (uranium fission converter-based beam) and the only one of such intense neutron beam in the Europe. Moreover implementation of the station would allow the development of research on a number of issues for researchers from all over the Europe. One of very important advantages of the station is undisturbed exploitation of the reactor and other vertical and horizontal channels. MARIA reactor operates 6000 hours per year and that amount of time will be achievable for research on the neutron station. It have to be underlined that new neutron station will work parallel to all another ventures. (authors)« less

Boron neutron capture therapy as new treatment for clear cell sarcoma: trial on different animal model.

PubMed

Andoh, Tooru; Fujimoto, Takuya; Sudo, Tamotsu; Suzuki, Minoru; Sakurai, Yoshinori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Takeuchi, Tamotsu; Sonobe, Hiroshi; Epstein, Alan L; Fukumori, Yoshinobu; Ono, Koji; Ichikawa, Hideki

2014-06-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mock-up experiment at Birmingham University for BNCT project of Osaka University--Neutron flux measurement with gold foil.

PubMed

Tamaki, S; Sakai, M; Yoshihashi, S; Manabe, M; Zushi, N; Murata, I; Hoashi, E; Kato, I; Kuri, S; Oshiro, S; Nagasaki, M; Horiike, H

2015-12-01

Mock-up experiment for development of accelerator based neutron source for Osaka University BNCT project was carried out at Birmingham University, UK. In this paper, spatial distribution of neutron flux intensity was evaluated by foil activation method. Validity of the design code system was confirmed by comparing measured gold foil activities with calculations. As a result, it was found that the epi-thermal neutron beam was well collimated by our neutron moderator assembly. Also, the design accuracy was evaluated to have less than 20% error. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generalized Optimal-State-Constraint Extended Kalman Filter (OSC-EKF)

DTIC Science & Technology

2017-02-01

ARL-TR-7948• FEB 2017 US Army Research Laboratory GeneralizedOptimal-State-Constraint ExtendedKalman Filter (OSC-EKF) by James M Maley, Kevin...originator. ARL-TR-7948• FEB 2017 US Army Research Laboratory GeneralizedOptimal-State-Constraint ExtendedKalman Filter (OSC-EKF) by James M Maley Weapons and...

A Low Cost Structurally Optimized Design for Diverse Filter Types

PubMed Central

Kazmi, Majida; Aziz, Arshad; Akhtar, Pervez; Ikram, Nassar

2016-01-01

A wide range of image processing applications deploys two dimensional (2D)-filters for performing diversified tasks such as image enhancement, edge detection, noise suppression, multi scale decomposition and compression etc. All of these tasks require multiple type of 2D-filters simultaneously to acquire the desired results. The resource hungry conventional approach is not a viable option for implementing these computationally intensive 2D-filters especially in a resource constraint environment. Thus it calls for optimized solutions. Mostly the optimization of these filters are based on exploiting structural properties. A common shortcoming of all previously reported optimized approaches is their restricted applicability only for a specific filter type. These narrow scoped solutions completely disregard the versatility attribute of advanced image processing applications and in turn offset their effectiveness while implementing a complete application. This paper presents an efficient framework which exploits the structural properties of 2D-filters for effectually reducing its computational cost along with an added advantage of versatility for supporting diverse filter types. A composite symmetric filter structure is introduced which exploits the identities of quadrant and circular T-symmetries in two distinct filter regions simultaneously. These T-symmetries effectually reduce the number of filter coefficients and consequently its multipliers count. The proposed framework at the same time empowers this composite filter structure with additional capabilities of realizing all of its Ψ-symmetry based subtypes and also its special asymmetric filters case. The two-fold optimized framework thus reduces filter computational cost up to 75% as compared to the conventional approach as well as its versatility attribute not only supports diverse filter types but also offers further cost reduction via resource sharing for sequential implementation of diversified image processing applications especially in a constraint environment. PMID:27832133

Improvement of LOD in Fluorescence Detection with Spectrally Nonuniform Background by Optimization of Emission Filtering.

PubMed

Galievsky, Victor A; Stasheuski, Alexander S; Krylov, Sergey N

2017-10-17

The limit-of-detection (LOD) in analytical instruments with fluorescence detection can be improved by reducing noise of optical background. Efficiently reducing optical background noise in systems with spectrally nonuniform background requires complex optimization of an emission filter-the main element of spectral filtration. Here, we introduce a filter-optimization method, which utilizes an expression for the signal-to-noise ratio (SNR) as a function of (i) all noise components (dark, shot, and flicker), (ii) emission spectrum of the analyte, (iii) emission spectrum of the optical background, and (iv) transmittance spectrum of the emission filter. In essence, the noise components and the emission spectra are determined experimentally and substituted into the expression. This leaves a single variable-the transmittance spectrum of the filter-which is optimized numerically by maximizing SNR. Maximizing SNR provides an accurate way of filter optimization, while a previously used approach based on maximizing a signal-to-background ratio (SBR) is the approximation that can lead to much poorer LOD specifically in detection of fluorescently labeled biomolecules. The proposed filter-optimization method will be an indispensable tool for developing new and improving existing fluorescence-detection systems aiming at ultimately low LOD.

Characteristics of a heavy water photoneutron source in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Danial, Salehi; Dariush, Sardari; M. Salehi, Jozani

2013-07-01

Bremsstrahlung photon beams produced by medical linear accelerators are currently the most commonly used method of radiation therapy for cancerous tumors. Photons with energies greater than 8-10 MeV potentially generate neutrons through photonuclear interactions in the accelerator's treatment head, patient's body, and treatment room ambient. Electrons impinging on a heavy target generate a cascade shower of bremsstrahlung photons, the energy spectrum of which shows an end point equal to the electron beam energy. By varying the target thickness, an optimum thickness exists for which, at the given electron energy, maximum photon flux is achievable. If a source of high-energy photons i.e. bremsstrahlung, is conveniently directed to a suitable D2O target, a novel approach for production of an acceptable flux of filterable photoneturons for boron neutron capture therapy (BNCT) application is possible. This study consists of two parts. 1. Comparison and assessment of deuterium photonuclear cross section data. 2. Evaluation of the heavy water photonuclear source.

Nonlinear Estimation With Sparse Temporal Measurements

DTIC Science & Technology

2016-09-01

Kalman filter , the extended Kalman filter (EKF) and unscented Kalman filter (UKF) are commonly used in practical application. The Kalman filter is an...optimal estimator for linear systems; the EKF and UKF are sub-optimal approximations of the Kalman filter . The EKF uses a first-order Taylor series...propagated covariance is compared for similarity with a Monte Carlo propagation. The similarity of the covariance matrices is shown to predict filter

A study of gamma-ray and neutron radiation in the interaction of a 2 MeV proton beam with various materials.

PubMed

Kasatov, D; Makarov, A; Shchudlo, I; Taskaev, S

2015-12-01

Epithermal neutron source based on a tandem accelerator with vacuum insulation and lithium target has been proposed, developed and operated in Budker Institute of Nuclear Physics. The source is regarded as a prototype of a future compact device suitable for carrying out BNCT in oncology centers. In this work the measurements of gamma-ray and neutron radiation are presented for the interaction of a 2 MeV proton beam with various materials (Li, C, F, Al, V, Ti, Cu, Mo, stainless steel, and Ta). The obtained results enabled the optimization of the neutron-generating target and the high energy beam transportation path. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improvement of the fringe analysis algorithm for wavelength scanning interferometry based on filter parameter optimization.

PubMed

Zhang, Tao; Gao, Feng; Muhamedsalih, Hussam; Lou, Shan; Martin, Haydn; Jiang, Xiangqian

2018-03-20

The phase slope method which estimates height through fringe pattern frequency and the algorithm which estimates height through the fringe phase are the fringe analysis algorithms widely used in interferometry. Generally they both extract the phase information by filtering the signal in frequency domain after Fourier transform. Among the numerous papers in the literature about these algorithms, it is found that the design of the filter, which plays an important role, has never been discussed in detail. This paper focuses on the filter design in these algorithms for wavelength scanning interferometry (WSI), trying to optimize the parameters to acquire the optimal results. The spectral characteristics of the interference signal are analyzed first. The effective signal is found to be narrow-band (near single frequency), and the central frequency is calculated theoretically. Therefore, the position of the filter pass-band is determined. The width of the filter window is optimized with the simulation to balance the elimination of the noise and the ringing of the filter. Experimental validation of the approach is provided, and the results agree very well with the simulation. The experiment shows that accuracy can be improved by optimizing the filter design, especially when the signal quality, i.e., the signal noise ratio (SNR), is low. The proposed method also shows the potential of improving the immunity to the environmental noise by adapting the signal to acquire the optimal results through designing an adaptive filter once the signal SNR can be estimated accurately.

DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

PubMed

Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

2016-03-01

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

PubMed

Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

2013-02-01

Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

Computational assessment of deep-seated tumor treatment capability of the 9Be(d,n)10B reaction for accelerator-based boron neutron capture therapy (AB-BNCT).

PubMed

Capoulat, M E; Minsky, D M; Kreiner, A J

2014-03-01

The 9Be(d,n)10B reaction was studied as an epithermal neutron source for brain tumor treatment through Boron Neutron Capture Therapy (BNCT). In BNCT, neutrons are classified according to their energies as thermal (<0.5 eV), epithermal (from 0.5 eV to 10 keV) or fast (>10 keV). For deep-seated tumors epithermal neutrons are needed. Since a fraction of the neutrons produced by this reaction are quite fast (up to 5-6 MeV, even for low-bombarding energies), an efficient beam shaping design is required. This task was carried out (1) by selecting the combinations of bombarding energy and target thickness that minimize the highest-energy neutron production; and (2) by the appropriate choice of the Beam Shaping Assembly (BSA) geometry, for each of the combinations found in (1). The BSA geometry was determined as the configuration that maximized the dose deliverable to the tumor in a 1 h treatment, within the constraints imposed by the healthy tissue dose adopted tolerance. Doses were calculated through the MCNP code. The highest dose deliverable to the tumor was found for an 8 μm target and a deuteron beam of 1.45 MeV. Tumor weighted doses ≥40 Gy can be delivered up to about 5 cm in depth, with a maximum value of 51 Gy at a depth of about 2 cm. This dose performance can be improved by relaxing the treatment time constraint and splitting the treatment into two 1-h sessions. These good treatment capabilities strengthen the prospects for a potential use of this reaction in BNCT. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Boron Neutron Capture Therapy for HER2+ breast cancers: A feasibility study evaluating BNCT for potential role in breast conservation therapies

NASA Astrophysics Data System (ADS)

Jenkins, Peter Anthony

A novel Boron Neutron Capture Therapy (BNCT) regimen for the treatment of HER2+ breast cancers has been proposed as an alternative to whole breast irradiation for breast conservation therapy patients. The proposed therapy regimen is based on the assumed production of boron delivery agents that would be synthesized from compounds of Trastuzumab (Herceptin ®) and oligomeric phosphate diesters (OPDs). The combination of the anti-HER2 monoclonal antibody and the high boron loading capability of OPDs has led to the assumption that boron could be delivered to the HER2+ cancer cells at Tumor to Healthy Tissue ratios (T:H) of up to 35:1 and boron concentrations above 50 μg/g. This significantly increased boron delivery efficiency has opened new BNCT possibilities. This proof of concept study examined treatment parameters derived as the results in previous efforts in the context of patient-specific geometry and compared calculated dose results to those observed during actual patient therapy. These results were based on dose calculations performed with a set of calculated Kerma coefficients derived from tissues specific to the regions of interest for breast cancer. A comparison was made of the dose to the tumor region, the patient's skin, and the peripheral organs. The results of this study demonstrated that, given the performance of the proposed boron delivery agent, the BNCT treatment regimen is feasible. The feasibility is based on the findings that the equivalent dose could be delivered to the treatment volume with less dose to the skin and peripheral organs. This is anticipated to improve the treatment outcomes by maintaining local control of tumor cells while reducing dose to healthy tissues.

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

PubMed Central

Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

2013-01-01

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

PubMed Central

Wada, Yuki; Hirose, Katsumi; Harada, Takaomi; Sato, Mariko; Watanabe, Tsubasa; Anbai, Akira; Hashimoto, Manabu; Takai, Yoshihiro

2018-01-01

Abstract Boron neutron capture therapy (BNCT) can potentially deliver high linear energy transfer particles to tumor cells without causing severe damage to surrounding normal tissue, and may thus be beneficial for cases with characteristics of infiltrative growth, which need a wider irradiation field, such as glioblastoma multiforme. Hypoxia is an important factor contributing to resistance to anticancer therapies such as radiotherapy and chemotherapy. In this study, we investigated the impact of oxygen status on 10B uptake in glioblastoma cells in vitro in order to evaluate the potential impact of local hypoxia on BNCT. T98G and A172 glioblastoma cells were used in the present study, and we examined the influence of oxygen concentration on cell viability, mRNA expression of L-amino acid transporter 1 (LAT1), and the uptake amount of 10B-BPA. T98G and A172 glioblastoma cells became quiescent after 72 h under 1% hypoxia but remained viable. Uptake of 10B-BPA, which is one of the agents for BNCT in clinical use, decreased linearly as oxygen levels were reduced from 20% through to 10%, 3% and 1%. Hypoxia with <10% O2 significantly decreased mRNA expression of LAT1 in both cell lines, indicating that reduced uptake of 10B-BPA in glioblastoma in hypoxic conditions may be due to reduced expression of this important transporter protein. Hypoxia inhibits 10B-BPA uptake in glioblastoma cells in a linear fashion, meaning that approaches to overcoming local tumor hypoxia may be an effective method of improving the success of BNCT treatment. PMID:29315429

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

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

Capuani, Silvia; Enrico Fermi Center, Rome; Gili, Tommaso

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on {sup 10}B(n,{alpha}){sup 7}Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for {sup 10}B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Twomore » L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.« less

First application of dynamic infrared imaging in boron neutron capture therapy for cutaneous malignant melanoma

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

Santa Cruz, G. A.; Gonzalez, S. J.; Bertotti, J.

2009-10-15

Purpose: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. Methods: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). Inmore » order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. Results: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 deg. C were observed in the larger nodules. Conclusions: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.« less

Deep learning architecture for iris recognition based on optimal Gabor filters and deep belief network

NASA Astrophysics Data System (ADS)

He, Fei; Han, Ye; Wang, Han; Ji, Jinchao; Liu, Yuanning; Ma, Zhiqiang

2017-03-01

Gabor filters are widely utilized to detect iris texture information in several state-of-the-art iris recognition systems. However, the proper Gabor kernels and the generative pattern of iris Gabor features need to be predetermined in application. The traditional empirical Gabor filters and shallow iris encoding ways are incapable of dealing with such complex variations in iris imaging including illumination, aging, deformation, and device variations. Thereby, an adaptive Gabor filter selection strategy and deep learning architecture are presented. We first employ particle swarm optimization approach and its binary version to define a set of data-driven Gabor kernels for fitting the most informative filtering bands, and then capture complex pattern from the optimal Gabor filtered coefficients by a trained deep belief network. A succession of comparative experiments validate that our optimal Gabor filters may produce more distinctive Gabor coefficients and our iris deep representations be more robust and stable than traditional iris Gabor codes. Furthermore, the depth and scales of the deep learning architecture are also discussed.

A robust approach to optimal matched filter design in ultrasonic non-destructive evaluation (NDE)

NASA Astrophysics Data System (ADS)

Li, Minghui; Hayward, Gordon

2017-02-01

The matched filter was demonstrated to be a powerful yet efficient technique to enhance defect detection and imaging in ultrasonic non-destructive evaluation (NDE) of coarse grain materials, provided that the filter was properly designed and optimized. In the literature, in order to accurately approximate the defect echoes, the design utilized the real excitation signals, which made it time consuming and less straightforward to implement in practice. In this paper, we present a more robust and flexible approach to optimal matched filter design using the simulated excitation signals, and the control parameters are chosen and optimized based on the real scenario of array transducer, transmitter-receiver system response, and the test sample, as a result, the filter response is optimized and depends on the material characteristics. Experiments on industrial samples are conducted and the results confirm the great benefits of the method.

Experiments to increase the parameters of the vacuum insulation tandem accelerator for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Kasatov, D. A.; Kolesnikov, J. A.; Koshkarev, A. M.; Kuznetsov, A. S.; Makarov, A. N.; Sokolova, E. O.; Sorokin, I. N.; Sycheva, T. V.; Taskaev, S. Yu.; Shchudlo, I. M.

2016-12-01

An epithermal neutron source that is based on a vacuum insulation tandem accelerator (VITA) and lithium target was created in the Budker Institute of Nuclear Physics for the development of boron neutron capture therapy (BNCT). A stationary proton beam with 2 MeV energy and 1.6 mA current has been obtained. To carry out BNCT, it is necessary to increase the beam parameters up to 2.3 MeV and 3 mA. Ways to increase the parameters of the proton beam have been proposed and discussed in this paper. The results of the experiments are presented.

Application of an ultraminiature thermal neutron monitor for irradiation field study of accelerator-based neutron capture therapy

PubMed Central

Ishikawa, Masayori; Tanaka, Kenichi; Endo, Satrou; Hoshi, Masaharu

2015-01-01

Abstract Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources. PMID:25589504

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

PubMed Central

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-01-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT. PMID:27759052

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study.

PubMed

Jung, Joo-Young; Yoon, Do-Kun; Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-06-13

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-10-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a Monte Carlo study

PubMed Central

Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-01-01

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy. PMID:28427153

Microdosimetric intercomparison of BNCT beams at BNL and MIT.

PubMed

Burmeister, Jay; Riley, Kent; Coderre, Jeffrey A; Harling, Otto K; Ma, Ruimei; Wielopolski, Lucian; Kota, Chandrasekhar; Maughan, Richard L

2003-08-01

Microdosimetric measurements have been performed at the clinical beam intensities in two epithermal neutron beams, the Brookhaven Medical Research Reactor and the M67 beam at the Massachusetts Institute of Technology Research Reactor, which have been used to treat patients with Boron Neutron Capture Therapy (BNCT). These measurements offer an independent assessment of the dosimetry used at these two facilities, as well as provide information about the radiation quality not obtainable from conventional macrodosimetric techniques. Moreover, they provide a direct measurement of the absorbed dose resulting from the BNC reaction. BNC absorbed doses measured within this study are approximately 15% lower than those estimated using foil activation at both MIT and BNL. Finally, an intercomparison of the characteristics and radiation quality of these two clinical beams is presented. The techniques described here allow an accurate quantitative comparison of the physical absorbed dose as well as a measure of the biological effectiveness of the absorbed dose delivered by different epithermal beams. No statistically significant differences were observed in the predicted RBEs of these two beams. The methodology presented here can help to facilitate the effective sharing of clinical results in an effort to demonstrate the clinical utility of BNCT.

Pattern recognition with composite correlation filters designed with multi-object combinatorial optimization

DOE PAGES

Awwal, Abdul; Diaz-Ramirez, Victor H.; Cuevas, Andres; ...

2014-10-23

Composite correlation filters are used for solving a wide variety of pattern recognition problems. These filters are given by a combination of several training templates chosen by a designer in an ad hoc manner. In this work, we present a new approach for the design of composite filters based on multi-objective combinatorial optimization. Given a vast search space of training templates, an iterative algorithm is used to synthesize a filter with an optimized performance in terms of several competing criteria. Furthermore, by employing a suggested binary-search procedure a filter bank with a minimum number of filters can be constructed, formore » a prespecified trade-off of performance metrics. Computer simulation results obtained with the proposed method in recognizing geometrically distorted versions of a target in cluttered and noisy scenes are discussed and compared in terms of recognition performance and complexity with existing state-of-the-art filters.« less

Pattern recognition with composite correlation filters designed with multi-object combinatorial optimization

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

Awwal, Abdul; Diaz-Ramirez, Victor H.; Cuevas, Andres

Composite correlation filters are used for solving a wide variety of pattern recognition problems. These filters are given by a combination of several training templates chosen by a designer in an ad hoc manner. In this work, we present a new approach for the design of composite filters based on multi-objective combinatorial optimization. Given a vast search space of training templates, an iterative algorithm is used to synthesize a filter with an optimized performance in terms of several competing criteria. Furthermore, by employing a suggested binary-search procedure a filter bank with a minimum number of filters can be constructed, formore » a prespecified trade-off of performance metrics. Computer simulation results obtained with the proposed method in recognizing geometrically distorted versions of a target in cluttered and noisy scenes are discussed and compared in terms of recognition performance and complexity with existing state-of-the-art filters.« less

Filter Selection for Optimizing the Spectral Sensitivity of Broadband Multispectral Cameras Based on Maximum Linear Independence.

PubMed

Li, Sui-Xian

2018-05-07

Previous research has shown that the effectiveness of selecting filter sets from among a large set of commercial broadband filters by a vector analysis method based on maximum linear independence (MLI). However, the traditional MLI approach is suboptimal due to the need to predefine the first filter of the selected filter set to be the maximum ℓ₂ norm among all available filters. An exhaustive imaging simulation with every single filter serving as the first filter is conducted to investigate the features of the most competent filter set. From the simulation, the characteristics of the most competent filter set are discovered. Besides minimization of the condition number, the geometric features of the best-performed filter set comprise a distinct transmittance peak along the wavelength axis of the first filter, a generally uniform distribution for the peaks of the filters and substantial overlaps of the transmittance curves of the adjacent filters. Therefore, the best-performed filter sets can be recognized intuitively by simple vector analysis and just a few experimental verifications. A practical two-step framework for selecting optimal filter set is recommended, which guarantees a significant enhancement of the performance of the systems. This work should be useful for optimizing the spectral sensitivity of broadband multispectral imaging sensors.

An optimal filter for short photoplethysmogram signals

PubMed Central

Liang, Yongbo; Elgendi, Mohamed; Chen, Zhencheng; Ward, Rabab

2018-01-01

A photoplethysmogram (PPG) contains a wealth of cardiovascular system information, and with the development of wearable technology, it has become the basic technique for evaluating cardiovascular health and detecting diseases. However, due to the varying environments in which wearable devices are used and, consequently, their varying susceptibility to noise interference, effective processing of PPG signals is challenging. Thus, the aim of this study was to determine the optimal filter and filter order to be used for PPG signal processing to make the systolic and diastolic waves more salient in the filtered PPG signal using the skewness quality index. Nine types of filters with 10 different orders were used to filter 219 (2.1s) short PPG signals. The signals were divided into three categories by PPG experts according to their noise levels: excellent, acceptable, or unfit. Results show that the Chebyshev II filter can improve the PPG signal quality more effectively than other types of filters and that the optimal order for the Chebyshev II filter is the 4th order. PMID:29714722

Progress in navigation filter estimate fusion and its application to spacecraft rendezvous

NASA Technical Reports Server (NTRS)

Carpenter, J. Russell

1994-01-01

A new derivation of an algorithm which fuses the outputs of two Kalman filters is presented within the context of previous research in this field. Unlike other works, this derivation clearly shows the combination of estimates to be optimal, minimizing the trace of the fused covariance matrix. The algorithm assumes that the filters use identical models, and are stable and operating optimally with respect to their own local measurements. Evidence is presented which indicates that the error ellipsoid derived from the covariance of the optimally fused estimate is contained within the intersections of the error ellipsoids of the two filters being fused. Modifications which reduce the algorithm's data transmission requirements are also presented, including a scalar gain approximation, a cross-covariance update formula which employs only the two contributing filters' autocovariances, and a form of the algorithm which can be used to reinitialize the two Kalman filters. A sufficient condition for using the optimally fused estimates to periodically reinitialize the Kalman filters in this fashion is presented and proved as a theorem. When these results are applied to an optimal spacecraft rendezvous problem, simulated performance results indicate that the use of optimally fused data leads to significantly improved robustness to initial target vehicle state errors. The following applications of estimate fusion methods to spacecraft rendezvous are also described: state vector differencing, and redundancy management.

Spectral optimized asymmetric segmented phase-only correlation filter.

PubMed

Leonard, I; Alfalou, A; Brosseau, C

2012-05-10

We suggest a new type of optimized composite filter, i.e., the asymmetric segmented phase-only filter (ASPOF), for improving the effectiveness of a VanderLugt correlator (VLC) when used for face identification. Basically, it consists in merging several reference images after application of a specific spectral optimization method. After segmentation of the spectral filter plane to several areas, each area is assigned to a single winner reference according to a new optimized criterion. The point of the paper is to show that this method offers a significant performance improvement on standard composite filters for face identification. We first briefly revisit composite filters [adapted, phase-only, inverse, compromise optimal, segmented, minimum average correlation energy, optimal trade-off maximum average correlation, and amplitude-modulated phase-only (AMPOF)], which are tools of choice for face recognition based on correlation techniques, and compare their performances with those of the ASPOF. We illustrate some of the drawbacks of current filters for several binary and grayscale image identifications. Next, we describe the optimization steps and introduce the ASPOF that can overcome these technical issues to improve the quality and the reliability of the correlation-based decision. We derive performance measures, i.e., PCE values and receiver operating characteristic curves, to confirm consistency of the results. We numerically find that this filter increases the recognition rate and decreases the false alarm rate. The results show that the discrimination of the ASPOF is comparable to that of the AMPOF, but the ASPOF is more robust than the trade-off maximum average correlation height against rotation and various types of noise sources. Our method has several features that make it amenable to experimental implementation using a VLC.

Grayscale Optical Correlator Workbench

NASA Technical Reports Server (NTRS)

Hanan, Jay; Zhou, Hanying; Chao, Tien-Hsin

2006-01-01

Grayscale Optical Correlator Workbench (GOCWB) is a computer program for use in automatic target recognition (ATR). GOCWB performs ATR with an accurate simulation of a hardware grayscale optical correlator (GOC). This simulation is performed to test filters that are created in GOCWB. Thus, GOCWB can be used as a stand-alone ATR software tool or in combination with GOC hardware for building (target training), testing, and optimization of filters. The software is divided into three main parts, denoted filter, testing, and training. The training part is used for assembling training images as input to a filter. The filter part is used for combining training images into a filter and optimizing that filter. The testing part is used for testing new filters and for general simulation of GOC output. The current version of GOCWB relies on the mathematical software tools from MATLAB binaries for performing matrix operations and fast Fourier transforms. Optimization of filters is based on an algorithm, known as OT-MACH, in which variables specified by the user are parameterized and the best filter is selected on the basis of an average result for correct identification of targets in multiple test images.

Study of low energy neutron beam formation based on GEANT4 simulations

NASA Astrophysics Data System (ADS)

Avagyan, R.; Avetisyan, R.; Ivanyan, V.; Kerobyan, I.

2017-07-01

The possibility of obtaining thermal/epithermal energy neutron beams using external protons from cyclotron C18/18 is studied based on GEANT4 simulations. This study will be the basis of the Beam Shaped Assembly (BSA) development for future Boron Neutron Capture Therapy (BNCT). Proton induced reactions on 9Be target are considered as a neutron source, and dependence of neutron yield on target thickness is investigated. The problem of reducing the ratio of gamma to neutron yields by inserting a lead sheet after the beryllium target is studied as well. By GEANT4 modeling the optimal thicknesses of 9Be target and lead absorber are determined and the design characteristics of beam shaping assembly, including the materials and thicknesses of reflector and moderator are considered.

Swarm Intelligence for Optimizing Hybridized Smoothing Filter in Image Edge Enhancement

NASA Astrophysics Data System (ADS)

Rao, B. Tirumala; Dehuri, S.; Dileep, M.; Vindhya, A.

In this modern era, image transmission and processing plays a major role. It would be impossible to retrieve information from satellite and medical images without the help of image processing techniques. Edge enhancement is an image processing step that enhances the edge contrast of an image or video in an attempt to improve its acutance. Edges are the representations of the discontinuities of image intensity functions. For processing these discontinuities in an image, a good edge enhancement technique is essential. The proposed work uses a new idea for edge enhancement using hybridized smoothening filters and we introduce a promising technique of obtaining best hybrid filter using swarm algorithms (Artificial Bee Colony (ABC), Particle Swarm Optimization (PSO) and Ant Colony Optimization (ACO)) to search for an optimal sequence of filters from among a set of rather simple, representative image processing filters. This paper deals with the analysis of the swarm intelligence techniques through the combination of hybrid filters generated by these algorithms for image edge enhancement.

Initial Ares I Bending Filter Design

NASA Technical Reports Server (NTRS)

Jang, Jiann-Woei; Bedrossian, Nazareth; Hall, Robert; Norris, H. Lee; Hall, Charles; Jackson, Mark

2007-01-01

The Ares-I launch vehicle represents a challenging flex-body structural environment for control system design. Software filtering of the inertial sensor output will be required to ensure control system stability and adequate performance. This paper presents a design methodology employing numerical optimization to develop the Ares-I bending filters. The filter design methodology was based on a numerical constrained optimization approach to maximize stability margins while meeting performance requirements. The resulting bending filter designs achieved stability by adding lag to the first structural frequency and hence phase stabilizing the first Ares-I flex mode. To minimize rigid body performance impacts, a priority was placed via constraints in the optimization algorithm to minimize bandwidth decrease with the addition of the bending filters. The bending filters provided here have been demonstrated to provide a stable first stage control system in both the frequency domain and the MSFC MAVERIC time domain simulation.

A plastic scintillator-based 2D thermal neutron mapping system for use in BNCT studies.

PubMed

Ghal-Eh, N; Green, S

2016-06-01

In this study, a scintillator-based measurement instrument is proposed which is capable of measuring a two-dimensional map of thermal neutrons within a phantom based on the detection of 2.22MeV gamma rays generated via nth+H→D+γ reaction. The proposed instrument locates around a small rectangular water phantom (14cm×15cm×20cm) used in Birmingham BNCT facility. The whole system has been simulated using MCNPX 2.6. The results confirm that the thermal flux peaks somewhere between 2cm and 4cm distance from the system entrance which is in agreement with previous studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy.

PubMed

Krstic, D; Markovic, V M; Jovanovic, Z; Milenkovic, B; Nikezic, D; Atanackovic, J

2014-10-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Measuring the stopping power of α particles in compact bone for BNCT

NASA Astrophysics Data System (ADS)

Provenzano, L.; Rodríguez, L. M.; Fregenal, D.; Bernardi, G.; Olivares, C.; Altieri, S.; Bortolussi, S.; González, S. J.

2015-01-01

The stopping power of α particles in thin films of decalcified sheep femur, in the range of 1.5 to 5.0 MeV incident energy, was measured by transmission of a backscattered beam from a heavy target. Additionally, the film elemental composition was determined by Rutherford Backscattering Spectrometry (RBS). These data will be used to measure boron concentration in thin films of bone using a spectrometry technique developed by the University of Pavia, since the concentration ratio between healthy tissue and tumor is of fundamental importance in Boron Neutron Capture Therapy (BNCT). The present experimental data are compared with numerical simulation results and with tabulated stopping power data of non-decalcified human bone.

Application of a Bonner sphere spectrometer for the determination of the angular neutron energy spectrum of an accelerator-based BNCT facility.

PubMed

Mirzajani, N; Ciolini, R; Di Fulvio, A; Esposito, J; d'Errico, F

2014-06-01

Experimental activities are underway at INFN Legnaro National Laboratories (LNL) (Padua, Italy) and Pisa University aimed at angular-dependent neutron energy spectra measurements produced by the (9)Be(p,xn) reaction, under a 5MeV proton beam. This work has been performed in the framework of INFN TRASCO-BNCT project. Bonner Sphere Spectrometer (BSS), based on (6)LiI (Eu) scintillator, was used with the shadow-cone technique. Proper unfolding codes, coupled to BSS response function calculated by Monte Carlo code, were finally used. The main results are reported here. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy.

PubMed

Kulvik, Martti; Kallio, Merja; Laakso, Juha; Vähätalo, Jyrki; Hermans, Raine; Järviluoma, Eija; Paetau, Anders; Rasilainen, Merja; Ruokonen, Inkeri; Seppälä, Matti; Jääskeläinen, Juha

2015-12-01

We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma and five schwannoma patients as a pre-BNCT feasibility study. With average tumour-to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and probably should, be developed to treat severe forms of the studied tumours. However, analysing 72 tumour and 250 blood samples yielded another finding: the plasma-to-whole blood boron concentrations varied with time, suggesting that the assumed constant boron ratio of 1:1 between normal brain tissue and whole blood deserves re-assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Software Would Largely Automate Design of Kalman Filter

NASA Technical Reports Server (NTRS)

Chuang, Jason C. H.; Negast, William J.

2005-01-01

Embedded Navigation Filter Automatic Designer (ENFAD) is a computer program being developed to automate the most difficult tasks in designing embedded software to implement a Kalman filter in a navigation system. The most difficult tasks are selection of error states of the filter and tuning of filter parameters, which are timeconsuming trial-and-error tasks that require expertise and rarely yield optimum results. An optimum selection of error states and filter parameters depends on navigation-sensor and vehicle characteristics, and on filter processing time. ENFAD would include a simulation module that would incorporate all possible error states with respect to a given set of vehicle and sensor characteristics. The first of two iterative optimization loops would vary the selection of error states until the best filter performance was achieved in Monte Carlo simulations. For a fixed selection of error states, the second loop would vary the filter parameter values until an optimal performance value was obtained. Design constraints would be satisfied in the optimization loops. Users would supply vehicle and sensor test data that would be used to refine digital models in ENFAD. Filter processing time and filter accuracy would be computed by ENFAD.

Optimal frequency domain textural edge detection filter

NASA Technical Reports Server (NTRS)

Townsend, J. K.; Shanmugan, K. S.; Frost, V. S.

1985-01-01

An optimal frequency domain textural edge detection filter is developed and its performance evaluated. For the given model and filter bandwidth, the filter maximizes the amount of output image energy placed within a specified resolution interval centered on the textural edge. Filter derivation is based on relating textural edge detection to tonal edge detection via the complex low-pass equivalent representation of narrowband bandpass signals and systems. The filter is specified in terms of the prolate spheroidal wave functions translated in frequency. Performance is evaluated using the asymptotic approximation version of the filter. This evaluation demonstrates satisfactory filter performance for ideal and nonideal textures. In addition, the filter can be adjusted to detect textural edges in noisy images at the expense of edge resolution.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PubMed

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-10-01

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

PubMed

Yokoyama, Kunio; Miyatake, Shin-Ichi; Kajimoto, Yoshinaga; Kawabata, Shinji; Doi, Atsushi; Yoshida, Toshiko; Okabe, Motonori; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko

2007-01-01

The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

Design and construction of shoulder recesses into the beam aperture shields for improved patient positioning at the FiR 1 BNCT facility.

PubMed

Auterinen, I; Kotiluoto, P; Hippeläinen, E; Kortesniemi, M; Seppälä, T; Serén, T; Mannila, V; Pöyry, P; Kankaanranta, L; Collan, J; Kouri, M; Joensuu, H; Savolainen, S

2004-11-01

Improvements have been made at the FiR 1 BNCT facility to ease the positioning of the patient with a tumor in the head and neck region into a lateral neutron beam. Shoulder recesses were constructed horizontally on both sides of the beam aperture. When shoulder recesses are not needed, they are filled with neutron attenuating filling blocks. MCNP simulations using an anthropomorphic human model BOMAB phantom showed that the main contribution to the increase in the effective dose to the patient's body due to the shoulder recesses was from the neutron dose of the arm. In a position when one arm is inside the shoulder recess, the maximal effective dose of the patient was estimated to be 0.7Sv/h. Dose measurements using the twin ionization chamber technique showed that the neutron dose increased on the sides as predicted by the MCNP model but there was no noticeable change in the gamma doses. When making the recesses into the lithium containing neutron shield material tritium contamination was confined using an underpressurized glove box and machine tools with local exhaust. The shoulder recesses give space for more flexible patient positioning and can be considered as a significant improvement of the Finnish BNCT facility.

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

Barth, R.F.; Matalka, K.Z.; Bailey, M.Q.

The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. MRA 27 cells (2 [times] 10[sup 5]) were implanted intracerebrally, and 30 days later, 120 mg of [sup 10]B-L-BPA were injected intraperitoneally into nude rats. Thirty days following implantation, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor. Six hours following administration of BPA, tumor, blood, and normal brain boron-10 levels were 23.7, 9.4, and 8.4 [mu]g/g respectively. Median survival time of untreatedmore » rats was 44 days compared to 76 days and 93 days for those receiving physical doses of 2.73 Gy and 3.64 Gy, respectively. Rats that have received both [sup 10]B-BPA and physical doses of 1.82, 2.73, or 3.64 Gy had median survival times of 170, 182, and 262 days, respectively. Forty percent of rats that had received the highest tumor dose (10.1 Gy) survived for > 300 days and in a replicate experiment 21% of the rats were longterm survivors (>220 days). Animals that received 12 Gy in a single dose or 18 Gy fractionated (2 Gy [times] 9) of gamma photons from a [sup 137]Cs source had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed no residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Significant prolongations in median survival time were noted in nude rats with intracerebral human melanoma that had received BNCT, thereby suggesting therapeutic efficacy. Large animal studies should be carried out to further assess BNCT of intracerebral melanoma before any human trials are contemplated. 49 refs., 7 figs., 2 tabs.« less

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

DOE PAGES

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.; ...

2017-08-01

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors

PubMed Central

Barth, Rolf F.; Yang, Weilian; Wu, Gong; Swindall, Michele; Byun, Youngjoo; Narayanasamy, Sureshbabu; Tjarks, Werner; Tordoff, Kevin; Moeschberger, Melvin L.; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

2008-01-01

The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl] thymidine, designated N5–2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(−) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of 10B-enriched N5–2OH were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15× reduction in tumor volume compared with TK1(−) controls. Based on these favorable results, BNCT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5–2OH by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 ± 7.2 days, 35.0 ± 3.3days, and 52.9 ± 8.9 days, respectively, for animals that received N5–2OH, BPA, or both. The differences between the survival plots of rats that received N5–2OH and BPA alone were highly significant (P = 0.0003). These data provide proof-of-principle that a 3CTA can function as a boron delivery agent for NCT. Further studies are planned to design and synthesize 3CTAs with enhanced chemical and biological properties, and increased therapeutic efficacy. PMID:18981415

Monte Carlo based protocol for cell survival and tumour control probability in BNCT.

PubMed

Ye, S J

1999-02-01

A mathematical model to calculate the theoretical cell survival probability (nominally, the cell survival fraction) is developed to evaluate preclinical treatment conditions for boron neutron capture therapy (BNCT). A treatment condition is characterized by the neutron beam spectra, single or bilateral exposure, and the choice of boron carrier drug (boronophenylalanine (BPA) or boron sulfhydryl hydride (BSH)). The cell survival probability defined from Poisson statistics is expressed with the cell-killing yield, the 10B(n,alpha)7Li reaction density, and the tolerable neutron fluence. The radiation transport calculation from the neutron source to tumours is carried out using Monte Carlo methods: (i) reactor-based BNCT facility modelling to yield the neutron beam library at an irradiation port; (ii) dosimetry to limit the neutron fluence below a tolerance dose (10.5 Gy-Eq); (iii) calculation of the 10B(n,alpha)7Li reaction density in tumours. A shallow surface tumour could be effectively treated by single exposure producing an average cell survival probability of 10(-3)-10(-5) for probable ranges of the cell-killing yield for the two drugs, while a deep tumour will require bilateral exposure to achieve comparable cell kills at depth. With very pure epithermal beams eliminating thermal, low epithermal and fast neutrons, the cell survival can be decreased by factors of 2-10 compared with the unmodified neutron spectrum. A dominant effect of cell-killing yield on tumour cell survival demonstrates the importance of choice of boron carrier drug. However, these calculations do not indicate an unambiguous preference for one drug, due to the large overlap of tumour cell survival in the probable ranges of the cell-killing yield for the two drugs. The cell survival value averaged over a bulky tumour volume is used to predict the overall BNCT therapeutic efficacy, using a simple model of tumour control probability (TCP).

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

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

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS)

PubMed Central

Chandra, S.; Ahmad, T.; Barth, R. F.; Kabalka, G. W.

2014-01-01

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 (10B) atoms to individual tumor cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumor cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B atoms reflects both bound and free pools of boron in individual tumor cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular scale resolution by clinically applicable techniques such as PET and MRI. In this study, secondary ion mass spectrometry (SIMS) based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high grade gliomas, recurrent tumors of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumor cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols. PMID:24684609

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS).

PubMed

Chandra, S; Ahmad, T; Barth, R F; Kabalka, G W

2014-06-01

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 ((10)B) atoms to individual tumour cells. Cell killing results from the (10)B (n, α)(7) Li neutron capture and fission reactions that occur if a sufficient number of (10)B atoms are localized in the tumour cells. Intranuclear (10)B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of (10)B atoms reflects both bound and free pools of boron in individual tumour cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular-scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high-grade gliomas, recurrent tumours of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

Sci-Thur AM: YIS – 07: Optimizing dual-energy x-ray parameters using a single filter for both high and low-energy images to enhance soft-tissue imaging

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

Bowman, Wesley; Sattarivand, Mike

Objective: To optimize dual-energy parameters of ExacTrac stereoscopic x-ray imaging system for lung SBRT patients Methods: Simulated spectra and a lung phantom were used to optimize filter material, thickness, kVps, and weighting factors to obtain bone subtracted dual-energy images. Spektr simulations were used to identify material in the atomic number (Z) range [3–83] based on a metric defined to separate spectrums of high and low energies. Both energies used the same filter due to time constraints of image acquisition in lung SBRT imaging. A lung phantom containing bone, soft tissue, and a tumor mimicking material was imaged with filter thicknessesmore » range [0–1] mm and kVp range [60–140]. A cost function based on contrast-to-noise-ratio of bone, soft tissue, and tumor, as well as image noise content, was defined to optimize filter thickness and kVp. Using the optimized parameters, dual-energy images of anthropomorphic Rando phantom were acquired and evaluated for bone subtraction. Imaging dose was measured with dual-energy technique using tin filtering. Results: Tin was the material of choice providing the best energy separation, non-toxicity, and non-reactiveness. The best soft-tissue-only image in the lung phantom was obtained using 0.3 mm tin and [140, 80] kVp pair. Dual-energy images of the Rando phantom had noticeable bone elimination when compared to no filtration. Dose was lower with tin filtering compared to no filtration. Conclusions: Dual-energy soft-tissue imaging is feasible using ExacTrac stereoscopic imaging system utilizing a single tin filter for both high and low energies and optimized acquisition parameters.« less

Joint Transmit and Receive Filter Optimization for Sub-Nyquist Delay-Doppler Estimation

NASA Astrophysics Data System (ADS)

Lenz, Andreas; Stein, Manuel S.; Swindlehurst, A. Lee

2018-05-01

In this article, a framework is presented for the joint optimization of the analog transmit and receive filter with respect to a parameter estimation problem. At the receiver, conventional signal processing systems restrict the two-sided bandwidth of the analog pre-filter $B$ to the rate of the analog-to-digital converter $f_s$ to comply with the well-known Nyquist-Shannon sampling theorem. In contrast, here we consider a transceiver that by design violates the common paradigm $B\\leq f_s$. To this end, at the receiver, we allow for a higher pre-filter bandwidth $B>f_s$ and study the achievable parameter estimation accuracy under a fixed sampling rate when the transmit and receive filter are jointly optimized with respect to the Bayesian Cram\\'{e}r-Rao lower bound. For the case of delay-Doppler estimation, we propose to approximate the required Fisher information matrix and solve the transceiver design problem by an alternating optimization algorithm. The presented approach allows us to explore the Pareto-optimal region spanned by transmit and receive filters which are favorable under a weighted mean squared error criterion. We also discuss the computational complexity of the obtained transceiver design by visualizing the resulting ambiguity function. Finally, we verify the performance of the optimized designs by Monte-Carlo simulations of a likelihood-based estimator.

Multi-Sensor Optimal Data Fusion Based on the Adaptive Fading Unscented Kalman Filter

PubMed Central

Gao, Bingbing; Hu, Gaoge; Gao, Shesheng; Gu, Chengfan

2018-01-01

This paper presents a new optimal data fusion methodology based on the adaptive fading unscented Kalman filter for multi-sensor nonlinear stochastic systems. This methodology has a two-level fusion structure: at the bottom level, an adaptive fading unscented Kalman filter based on the Mahalanobis distance is developed and serves as local filters to improve the adaptability and robustness of local state estimations against process-modeling error; at the top level, an unscented transformation-based multi-sensor optimal data fusion for the case of N local filters is established according to the principle of linear minimum variance to calculate globally optimal state estimation by fusion of local estimations. The proposed methodology effectively refrains from the influence of process-modeling error on the fusion solution, leading to improved adaptability and robustness of data fusion for multi-sensor nonlinear stochastic systems. It also achieves globally optimal fusion results based on the principle of linear minimum variance. Simulation and experimental results demonstrate the efficacy of the proposed methodology for INS/GNSS/CNS (inertial navigation system/global navigation satellite system/celestial navigation system) integrated navigation. PMID:29415509

Multi-Sensor Optimal Data Fusion Based on the Adaptive Fading Unscented Kalman Filter.

PubMed

Gao, Bingbing; Hu, Gaoge; Gao, Shesheng; Zhong, Yongmin; Gu, Chengfan

2018-02-06

This paper presents a new optimal data fusion methodology based on the adaptive fading unscented Kalman filter for multi-sensor nonlinear stochastic systems. This methodology has a two-level fusion structure: at the bottom level, an adaptive fading unscented Kalman filter based on the Mahalanobis distance is developed and serves as local filters to improve the adaptability and robustness of local state estimations against process-modeling error; at the top level, an unscented transformation-based multi-sensor optimal data fusion for the case of N local filters is established according to the principle of linear minimum variance to calculate globally optimal state estimation by fusion of local estimations. The proposed methodology effectively refrains from the influence of process-modeling error on the fusion solution, leading to improved adaptability and robustness of data fusion for multi-sensor nonlinear stochastic systems. It also achieves globally optimal fusion results based on the principle of linear minimum variance. Simulation and experimental results demonstrate the efficacy of the proposed methodology for INS/GNSS/CNS (inertial navigation system/global navigation satellite system/celestial navigation system) integrated navigation.

INEL BNCT Research Program Annual Report 1993

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

Venhuizen, J.R.

1994-08-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy Research Program for calendar year 1993. Contributions from all the principal investigators are included, covering chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, boron drug analysis), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (tissue and efficacy studies of small and large animal models). Information on the potential toxicity of borocaptate sodium and boronophenylalanine is presented. Results of 21 spontaneous-tumor-bearing dogsmore » that have been treated with boron neutron capture therapy at the Brookhaven National Laboratory are updated. Boron-containing drug purity verification is discussed in some detail. Advances in magnetic resonance imaging of boron in vivo are discussed. Several boron-carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors is presented. Measurement of the epithermal-neutron flux of the Petten (The Netherlands) High Flux Reactor beam (HFB11B), and comparison to predictions are shown.« less

Robust Controller for Turbulent and Convective Boundary Layers

DTIC Science & Technology

2006-08-01

filter and an optimal regulator. The Kalman filter equation and the optimal regulator equation corresponding to the state-space equations, (2.20), are...separate steady-state algebraic Riccati equations. The Kalman filter is used here as a state observer rather than as an estimator since no noises are...2001) which will not be repeated here. For robustness, in the design, the Kalman filter input matrix G has been set equal to the control input

Adaptive torque estimation of robot joint with harmonic drive transmission

NASA Astrophysics Data System (ADS)

Shi, Zhiguo; Li, Yuankai; Liu, Guangjun

2017-11-01

Robot joint torque estimation using input and output position measurements is a promising technique, but the result may be affected by the load variation of the joint. In this paper, a torque estimation method with adaptive robustness and optimality adjustment according to load variation is proposed for robot joint with harmonic drive transmission. Based on a harmonic drive model and a redundant adaptive robust Kalman filter (RARKF), the proposed approach can adapt torque estimation filtering optimality and robustness to the load variation by self-tuning the filtering gain and self-switching the filtering mode between optimal and robust. The redundant factor of RARKF is designed as a function of the motor current for tolerating the modeling error and load-dependent filtering mode switching. The proposed joint torque estimation method has been experimentally studied in comparison with a commercial torque sensor and two representative filtering methods. The results have demonstrated the effectiveness of the proposed torque estimation technique.

INEL BNCT Research Program, March/April 1992

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

Venhuizen, J.R.

1992-09-01

This report presents summaries for two months of current research for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murino screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor call culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronopheoylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, andmore » noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.« less

First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and clinical outcome.

PubMed

González, S J; Bonomi, M R; Santa Cruz, G A; Blaumann, H R; Calzetta Larrieu, O A; Menéndez, P; Jiménez Rebagliati, R; Longhino, J; Feld, D B; Dagrosa, M A; Argerich, C; Castiglia, S G; Batistoni, D A; Liberman, S J; Roth, B M C

2004-11-01

A Phase I/II protocol for treating cutaneuos melanomas with BNCT was designed in Argentina by the Comisión Nacional de Energía Atómica and the medical center Instituto Roffo. The first of a cohort of thirty planned patients was treated on October 9, 2003. This article depicts the protocol-based procedure and describes the first clinical case, treatment regime and planning, patient irradiation, retrospective dosimetric analysis and clinical outcome. Considering the low acute skin toxicity and the complete response in 21 of the 25 subcutaneous melanoma nodules treated, a second irradiation was performed in a different location of the extremity of the same patient. The corresponding clinical outcome is still under evaluation.

Optimal Divergence-Free Hatch Filter for GNSS Single-Frequency Measurement.

PubMed

Park, Byungwoon; Lim, Cheolsoon; Yun, Youngsun; Kim, Euiho; Kee, Changdon

2017-02-24

The Hatch filter is a code-smoothing technique that uses the variation of the carrier phase. It can effectively reduce the noise of a pseudo-range with a very simple filter construction, but it occasionally causes an ionosphere-induced error for low-lying satellites. Herein, we propose an optimal single-frequency (SF) divergence-free Hatch filter that uses a satellite-based augmentation system (SBAS) message to reduce the ionospheric divergence and applies the optimal smoothing constant for its smoothing window width. According to the data-processing results, the overall performance of the proposed filter is comparable to that of the dual frequency (DF) divergence-free Hatch filter. Moreover, it can reduce the horizontal error of 57 cm to 37 cm and improve the vertical accuracy of the conventional Hatch filter by 25%. Considering that SF receivers dominate the global navigation satellite system (GNSS) market and that most of these receivers include the SBAS function, the filter suggested in this paper is of great value in that it can make the differential GPS (DGPS) performance of the low-cost SF receivers comparable to that of DF receivers.

Optimal Divergence-Free Hatch Filter for GNSS Single-Frequency Measurement

PubMed Central

Park, Byungwoon; Lim, Cheolsoon; Yun, Youngsun; Kim, Euiho; Kee, Changdon

2017-01-01

The Hatch filter is a code-smoothing technique that uses the variation of the carrier phase. It can effectively reduce the noise of a pseudo-range with a very simple filter construction, but it occasionally causes an ionosphere-induced error for low-lying satellites. Herein, we propose an optimal single-frequency (SF) divergence-free Hatch filter that uses a satellite-based augmentation system (SBAS) message to reduce the ionospheric divergence and applies the optimal smoothing constant for its smoothing window width. According to the data-processing results, the overall performance of the proposed filter is comparable to that of the dual frequency (DF) divergence-free Hatch filter. Moreover, it can reduce the horizontal error of 57 cm to 37 cm and improve the vertical accuracy of the conventional Hatch filter by 25%. Considering that SF receivers dominate the global navigation satellite system (GNSS) market and that most of these receivers include the SBAS function, the filter suggested in this paper is of great value in that it can make the differential GPS (DGPS) performance of the low-cost SF receivers comparable to that of DF receivers. PMID:28245584

Optical Correlation of Images With Signal-Dependent Noise Using Constrained-Modulation Filter Devices

NASA Technical Reports Server (NTRS)

Downie, John D.

1995-01-01

Images with signal-dependent noise present challenges beyond those of images with additive white or colored signal-independent noise in terms of designing the optimal 4-f correlation filter that maximizes correlation-peak signal-to-noise ratio, or combinations of correlation-peak metrics. Determining the proper design becomes more difficult when the filter is to be implemented on a constrained-modulation spatial light modulator device. The design issues involved for updatable optical filters for images with signal-dependent film-grain noise and speckle noise are examined. It is shown that although design of the optimal linear filter in the Fourier domain is impossible for images with signal-dependent noise, proper nonlinear preprocessing of the images allows the application of previously developed design rules for optimal filters to be implemented on constrained-modulation devices. Thus the nonlinear preprocessing becomes necessary for correlation in optical systems with current spatial light modulator technology. These results are illustrated with computer simulations of images with signal-dependent noise correlated with binary-phase-only filters and ternary-phase-amplitude filters.

New estimation architecture for multisensor data fusion

NASA Astrophysics Data System (ADS)

Covino, Joseph M.; Griffiths, Barry E.

1991-07-01

This paper describes a novel method of hierarchical asynchronous distributed filtering called the Net Information Approach (NIA). The NIA is a Kalman-filter-based estimation scheme for spatially distributed sensors which must retain their local optimality yet require a nearly optimal global estimate. The key idea of the NIA is that each local sensor-dedicated filter tells the global filter 'what I've learned since the last local-to-global transmission,' whereas in other estimation architectures the local-to-global transmission consists of 'what I think now.' An algorithm based on this idea has been demonstrated on a small-scale target-tracking problem with many encouraging results. Feasibility of this approach was demonstrated by comparing NIA performance to an optimal centralized Kalman filter (lower bound) via Monte Carlo simulations.

PSO Algorithm Particle Filters for Improving the Performance of Lane Detection and Tracking Systems in Difficult Roads

PubMed Central

Cheng, Wen-Chang

2012-01-01

In this paper we propose a robust lane detection and tracking method by combining particle filters with the particle swarm optimization method. This method mainly uses the particle filters to detect and track the local optimum of the lane model in the input image and then seeks the global optimal solution of the lane model by a particle swarm optimization method. The particle filter can effectively complete lane detection and tracking in complicated or variable lane environments. However, the result obtained is usually a local optimal system status rather than the global optimal system status. Thus, the particle swarm optimization method is used to further refine the global optimal system status in all system statuses. Since the particle swarm optimization method is a global optimization algorithm based on iterative computing, it can find the global optimal lane model by simulating the food finding way of fish school or insects under the mutual cooperation of all particles. In verification testing, the test environments included highways and ordinary roads as well as straight and curved lanes, uphill and downhill lanes, lane changes, etc. Our proposed method can complete the lane detection and tracking more accurately and effectively then existing options. PMID:23235453

A Unified Fisher's Ratio Learning Method for Spatial Filter Optimization.

PubMed

Li, Xinyang; Guan, Cuntai; Zhang, Haihong; Ang, Kai Keng

To detect the mental task of interest, spatial filtering has been widely used to enhance the spatial resolution of electroencephalography (EEG). However, the effectiveness of spatial filtering is undermined due to the significant nonstationarity of EEG. Based on regularization, most of the conventional stationary spatial filter design methods address the nonstationarity at the cost of the interclass discrimination. Moreover, spatial filter optimization is inconsistent with feature extraction when EEG covariance matrices could not be jointly diagonalized due to the regularization. In this paper, we propose a novel framework for a spatial filter design. With Fisher's ratio in feature space directly used as the objective function, the spatial filter optimization is unified with feature extraction. Given its ratio form, the selection of the regularization parameter could be avoided. We evaluate the proposed method on a binary motor imagery data set of 16 subjects, who performed the calibration and test sessions on different days. The experimental results show that the proposed method yields improvement in classification performance for both single broadband and filter bank settings compared with conventional nonunified methods. We also provide a systematic attempt to compare different objective functions in modeling data nonstationarity with simulation studies.To detect the mental task of interest, spatial filtering has been widely used to enhance the spatial resolution of electroencephalography (EEG). However, the effectiveness of spatial filtering is undermined due to the significant nonstationarity of EEG. Based on regularization, most of the conventional stationary spatial filter design methods address the nonstationarity at the cost of the interclass discrimination. Moreover, spatial filter optimization is inconsistent with feature extraction when EEG covariance matrices could not be jointly diagonalized due to the regularization. In this paper, we propose a novel framework for a spatial filter design. With Fisher's ratio in feature space directly used as the objective function, the spatial filter optimization is unified with feature extraction. Given its ratio form, the selection of the regularization parameter could be avoided. We evaluate the proposed method on a binary motor imagery data set of 16 subjects, who performed the calibration and test sessions on different days. The experimental results show that the proposed method yields improvement in classification performance for both single broadband and filter bank settings compared with conventional nonunified methods. We also provide a systematic attempt to compare different objective functions in modeling data nonstationarity with simulation studies.

Cellular traction force recovery: An optimal filtering approach in two-dimensional Fourier space.

PubMed

Huang, Jianyong; Qin, Lei; Peng, Xiaoling; Zhu, Tao; Xiong, Chunyang; Zhang, Youyi; Fang, Jing

2009-08-21

Quantitative estimation of cellular traction has significant physiological and clinical implications. As an inverse problem, traction force recovery is essentially susceptible to noise in the measured displacement data. For traditional procedure of Fourier transform traction cytometry (FTTC), noise amplification is accompanied in the force reconstruction and small tractions cannot be recovered from the displacement field with low signal-noise ratio (SNR). To improve the FTTC process, we develop an optimal filtering scheme to suppress the noise in the force reconstruction procedure. In the framework of the Wiener filtering theory, four filtering parameters are introduced in two-dimensional Fourier space and their analytical expressions are derived in terms of the minimum-mean-squared-error (MMSE) optimization criterion. The optimal filtering approach is validated with simulations and experimental data associated with the adhesion of single cardiac myocyte to elastic substrate. The results indicate that the proposed method can highly enhance SNR of the recovered forces to reveal tiny tractions in cell-substrate interaction.

GaN nanostructure design for optimal dislocation filtering

NASA Astrophysics Data System (ADS)

Liang, Zhiwen; Colby, Robert; Wildeson, Isaac H.; Ewoldt, David A.; Sands, Timothy D.; Stach, Eric A.; García, R. Edwin

2010-10-01

The effect of image forces in GaN pyramidal nanorod structures is investigated to develop dislocation-free light emitting diodes (LEDs). A model based on the eigenstrain method and nonlocal stress is developed to demonstrate that the pyramidal nanorod efficiently ejects dislocations out of the structure. Two possible regimes of filtering behavior are found: (1) cap-dominated and (2) base-dominated. The cap-dominated regime is shown to be the more effective filtering mechanism. Optimal ranges of fabrication parameters that favor a dislocation-free LED are predicted and corroborated by resorting to available experimental evidence. The filtering probability is summarized as a function of practical processing parameters: the nanorod radius and height. The results suggest an optimal nanorod geometry with a radius of ˜50b (26 nm) and a height of ˜125b (65 nm), in which b is the magnitude of the Burgers vector for the GaN system studied. A filtering probability of greater than 95% is predicted for the optimal geometry.

Weighted finite impulse response filter for chromatic dispersion equalization in coherent optical fiber communication systems

NASA Astrophysics Data System (ADS)

Zeng, Ziyi; Yang, Aiying; Guo, Peng; Feng, Lihui

2018-01-01

Time-domain CD equalization using finite impulse response (FIR) filter is now a common approach for coherent optical fiber communication systems. The complex weights of FIR taps are calculated from a truncated impulse response of the CD transfer function, and the modulus of the complex weights is constant. In our work, we take the limited bandwidth of a single channel signal into account and propose weighted FIRs to improve the performance of CD equalization. The key in weighted FIR filters is the selection and optimization of weighted functions. In order to present the performance of different types of weighted FIR filters, a square-root raised cosine FIR (SRRC-FIR) and a Gaussian FIR (GS-FIR) are investigated. The optimization of square-root raised cosine FIR and Gaussian FIR are made in term of the bit rate error (BER) of QPSK and 16QAM coherent detection signal. The results demonstrate that the optimized parameters of the weighted filters are independent of the modulation format, symbol rate and the length of transmission fiber. With the optimized weighted FIRs, the BER of CD equalization signal is decreased significantly. Although this paper has investigated two types of weighted FIR filters, i.e. SRRC-FIR filter and GS-FIR filter, the principle of weighted FIR can also be extended to other symmetric functions super Gaussian function, hyperbolic secant function and etc.

Design of order statistics filters using feedforward neural networks

NASA Astrophysics Data System (ADS)

Maslennikova, Yu. S.; Bochkarev, V. V.

2016-08-01

In recent years significant progress have been made in the development of nonlinear data processing techniques. Such techniques are widely used in digital data filtering and image enhancement. Many of the most effective nonlinear filters based on order statistics. The widely used median filter is the best known order statistic filter. Generalized form of these filters could be presented based on Lloyd's statistics. Filters based on order statistics have excellent robustness properties in the presence of impulsive noise. In this paper, we present special approach for synthesis of order statistics filters using artificial neural networks. Optimal Lloyd's statistics are used for selecting of initial weights for the neural network. Adaptive properties of neural networks provide opportunities to optimize order statistics filters for data with asymmetric distribution function. Different examples demonstrate the properties and performance of presented approach.

Monte Carlo simulations and benchmark measurements on the response of TE(TE) and Mg(Ar) ionization chambers in photon, electron and neutron beams

NASA Astrophysics Data System (ADS)

Lin, Yi-Chun; Huang, Tseng-Te; Liu, Yuan-Hao; Chen, Wei-Lin; Chen, Yen-Fu; Wu, Shu-Wei; Nievaart, Sander; Jiang, Shiang-Huei

2015-06-01

The paired ionization chambers (ICs) technique is commonly employed to determine neutron and photon doses in radiology or radiotherapy neutron beams, where neutron dose shows very strong dependence on the accuracy of accompanying high energy photon dose. During the dose derivation, it is an important issue to evaluate the photon and electron response functions of two commercially available ionization chambers, denoted as TE(TE) and Mg(Ar), used in our reactor based epithermal neutron beam. Nowadays, most perturbation corrections for accurate dose determination and many treatment planning systems are based on the Monte Carlo technique. We used general purposed Monte Carlo codes, MCNP5, EGSnrc, FLUKA or GEANT4 for benchmark verifications among them and carefully measured values for a precise estimation of chamber current from absorbed dose rate of cavity gas. Also, energy dependent response functions of two chambers were calculated in a parallel beam with mono-energies from 20 keV to 20 MeV photons and electrons by using the optimal simple spherical and detailed IC models. The measurements were performed in the well-defined (a) four primary M-80, M-100, M120 and M150 X-ray calibration fields, (b) primary 60Co calibration beam, (c) 6 MV and 10 MV photon, (d) 6 MeV and 18 MeV electron LINACs in hospital and (e) BNCT clinical trials neutron beam. For the TE(TE) chamber, all codes were almost identical over the whole photon energy range. In the Mg(Ar) chamber, MCNP5 showed lower response than other codes for photon energy region below 0.1 MeV and presented similar response above 0.2 MeV (agreed within 5% in the simple spherical model). With the increase of electron energy, the response difference between MCNP5 and other codes became larger in both chambers. Compared with the measured currents, MCNP5 had the difference from the measurement data within 5% for the 60Co, 6 MV, 10 MV, 6 MeV and 18 MeV LINACs beams. But for the Mg(Ar) chamber, the derivations reached 7.8-16.5% below 120 kVp X-ray beams. In this study, we were especially interested in BNCT doses where low energy photon contribution is less to ignore, MCNP model is recognized as the most suitable to simulate wide photon-electron and neutron energy distributed responses of the paired ICs. Also, MCNP provides the best prediction of BNCT source adjustment by the detector's neutron and photon responses.

The optimal digital filters of sine and cosine transforms for geophysical transient electromagnetic method

NASA Astrophysics Data System (ADS)

Zhao, Yun-wei; Zhu, Zi-qiang; Lu, Guang-yin; Han, Bo

2018-03-01

The sine and cosine transforms implemented with digital filters have been used in the Transient electromagnetic methods for a few decades. Kong (2007) proposed a method of obtaining filter coefficients, which are computed in the sample domain by Hankel transform pair. However, the curve shape of Hankel transform pair changes with a parameter, which usually is set to be 1 or 3 in the process of obtaining the digital filter coefficients of sine and cosine transforms. First, this study investigates the influence of the parameter on the digital filter algorithm of sine and cosine transforms based on the digital filter algorithm of Hankel transform and the relationship between the sine, cosine function and the ±1/2 order Bessel function of the first kind. The results show that the selection of the parameter highly influences the precision of digital filter algorithm. Second, upon the optimal selection of the parameter, it is found that an optimal sampling interval s also exists to achieve the best precision of digital filter algorithm. Finally, this study proposes four groups of sine and cosine transform digital filter coefficients with different length, which may help to develop the digital filter algorithm of sine and cosine transforms, and promote its application.

Optimal nonlinear filtering using the finite-volume method

NASA Astrophysics Data System (ADS)

Fox, Colin; Morrison, Malcolm E. K.; Norton, Richard A.; Molteno, Timothy C. A.

2018-01-01

Optimal sequential inference, or filtering, for the state of a deterministic dynamical system requires simulation of the Frobenius-Perron operator, that can be formulated as the solution of a continuity equation. For low-dimensional, smooth systems, the finite-volume numerical method provides a solution that conserves probability and gives estimates that converge to the optimal continuous-time values, while a Courant-Friedrichs-Lewy-type condition assures that intermediate discretized solutions remain positive density functions. This method is demonstrated in an example of nonlinear filtering for the state of a simple pendulum, with comparison to results using the unscented Kalman filter, and for a case where rank-deficient observations lead to multimodal probability distributions.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

PubMed Central

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-01-01

Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID:27401411

Modeling error analysis of stationary linear discrete-time filters

NASA Technical Reports Server (NTRS)

Patel, R.; Toda, M.

1977-01-01

The performance of Kalman-type, linear, discrete-time filters in the presence of modeling errors is considered. The discussion is limited to stationary performance, and bounds are obtained for the performance index, the mean-squared error of estimates for suboptimal and optimal (Kalman) filters. The computation of these bounds requires information on only the model matrices and the range of errors for these matrices. Consequently, a design can easily compare the performance of a suboptimal filter with that of the optimal filter, when only the range of errors in the elements of the model matrices is available.

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

Efficient and Accurate Optimal Linear Phase FIR Filter Design Using Opposition-Based Harmony Search Algorithm

PubMed Central

Saha, S. K.; Dutta, R.; Choudhury, R.; Kar, R.; Mandal, D.; Ghoshal, S. P.

2013-01-01

In this paper, opposition-based harmony search has been applied for the optimal design of linear phase FIR filters. RGA, PSO, and DE have also been adopted for the sake of comparison. The original harmony search algorithm is chosen as the parent one, and opposition-based approach is applied. During the initialization, randomly generated population of solutions is chosen, opposite solutions are also considered, and the fitter one is selected as a priori guess. In harmony memory, each such solution passes through memory consideration rule, pitch adjustment rule, and then opposition-based reinitialization generation jumping, which gives the optimum result corresponding to the least error fitness in multidimensional search space of FIR filter design. Incorporation of different control parameters in the basic HS algorithm results in the balancing of exploration and exploitation of search space. Low pass, high pass, band pass, and band stop FIR filters are designed with the proposed OHS and other aforementioned algorithms individually for comparative optimization performance. A comparison of simulation results reveals the optimization efficacy of the OHS over the other optimization techniques for the solution of the multimodal, nondifferentiable, nonlinear, and constrained FIR filter design problems. PMID:23844390

Efficient and accurate optimal linear phase FIR filter design using opposition-based harmony search algorithm.

PubMed

Saha, S K; Dutta, R; Choudhury, R; Kar, R; Mandal, D; Ghoshal, S P

2013-01-01

In this paper, opposition-based harmony search has been applied for the optimal design of linear phase FIR filters. RGA, PSO, and DE have also been adopted for the sake of comparison. The original harmony search algorithm is chosen as the parent one, and opposition-based approach is applied. During the initialization, randomly generated population of solutions is chosen, opposite solutions are also considered, and the fitter one is selected as a priori guess. In harmony memory, each such solution passes through memory consideration rule, pitch adjustment rule, and then opposition-based reinitialization generation jumping, which gives the optimum result corresponding to the least error fitness in multidimensional search space of FIR filter design. Incorporation of different control parameters in the basic HS algorithm results in the balancing of exploration and exploitation of search space. Low pass, high pass, band pass, and band stop FIR filters are designed with the proposed OHS and other aforementioned algorithms individually for comparative optimization performance. A comparison of simulation results reveals the optimization efficacy of the OHS over the other optimization techniques for the solution of the multimodal, nondifferentiable, nonlinear, and constrained FIR filter design problems.

Optimized Multi-Spectral Filter Array Based Imaging of Natural Scenes.

PubMed

Li, Yuqi; Majumder, Aditi; Zhang, Hao; Gopi, M

2018-04-12

Multi-spectral imaging using a camera with more than three channels is an efficient method to acquire and reconstruct spectral data and is used extensively in tasks like object recognition, relighted rendering, and color constancy. Recently developed methods are used to only guide content-dependent filter selection where the set of spectral reflectances to be recovered are known a priori. We present the first content-independent spectral imaging pipeline that allows optimal selection of multiple channels. We also present algorithms for optimal placement of the channels in the color filter array yielding an efficient demosaicing order resulting in accurate spectral recovery of natural reflectance functions. These reflectance functions have the property that their power spectrum statistically exhibits a power-law behavior. Using this property, we propose power-law based error descriptors that are minimized to optimize the imaging pipeline. We extensively verify our models and optimizations using large sets of commercially available wide-band filters to demonstrate the greater accuracy and efficiency of our multi-spectral imaging pipeline over existing methods.

Optimized Multi-Spectral Filter Array Based Imaging of Natural Scenes

PubMed Central

Li, Yuqi; Majumder, Aditi; Zhang, Hao; Gopi, M.

2018-01-01

Multi-spectral imaging using a camera with more than three channels is an efficient method to acquire and reconstruct spectral data and is used extensively in tasks like object recognition, relighted rendering, and color constancy. Recently developed methods are used to only guide content-dependent filter selection where the set of spectral reflectances to be recovered are known a priori. We present the first content-independent spectral imaging pipeline that allows optimal selection of multiple channels. We also present algorithms for optimal placement of the channels in the color filter array yielding an efficient demosaicing order resulting in accurate spectral recovery of natural reflectance functions. These reflectance functions have the property that their power spectrum statistically exhibits a power-law behavior. Using this property, we propose power-law based error descriptors that are minimized to optimize the imaging pipeline. We extensively verify our models and optimizations using large sets of commercially available wide-band filters to demonstrate the greater accuracy and efficiency of our multi-spectral imaging pipeline over existing methods. PMID:29649114

Optimizing of a high-order digital filter using PSO algorithm

NASA Astrophysics Data System (ADS)

Xu, Fuchun

2018-04-01

A self-adaptive high-order digital filter, which offers opportunity to simplify the process of tuning parameters and further improve the noise performance, is presented in this paper. The parameters of traditional digital filter are mainly tuned by complex calculation, whereas this paper presents a 5th order digital filter to obtain outstanding performance and the parameters of the proposed filter are optimized by swarm intelligent algorithm. Simulation results with respect to the proposed 5th order digital filter, SNR>122dB and the noise floor under -170dB are obtained in frequency range of [5-150Hz]. In further simulation, the robustness of the proposed 5th order digital is analyzed.

Analysis of multidimensional difference-of-Gaussians filters in terms of directly observable parameters.

PubMed

Cope, Davis; Blakeslee, Barbara; McCourt, Mark E

2013-05-01

The difference-of-Gaussians (DOG) filter is a widely used model for the receptive field of neurons in the retina and lateral geniculate nucleus (LGN) and is a potential model in general for responses modulated by an excitatory center with an inhibitory surrounding region. A DOG filter is defined by three standard parameters: the center and surround sigmas (which define the variance of the radially symmetric Gaussians) and the balance (which defines the linear combination of the two Gaussians). These parameters are not directly observable and are typically determined by nonlinear parameter estimation methods applied to the frequency response function. DOG filters show both low-pass (optimal response at zero frequency) and bandpass (optimal response at a nonzero frequency) behavior. This paper reformulates the DOG filter in terms of a directly observable parameter, the zero-crossing radius, and two new (but not directly observable) parameters. In the two-dimensional parameter space, the exact region corresponding to bandpass behavior is determined. A detailed description of the frequency response characteristics of the DOG filter is obtained. It is also found that the directly observable optimal frequency and optimal gain (the ratio of the response at optimal frequency to the response at zero frequency) provide an alternate coordinate system for the bandpass region. Altogether, the DOG filter and its three standard implicit parameters can be determined by three directly observable values. The two-dimensional bandpass region is a potential tool for the analysis of populations of DOG filters (for example, populations of neurons in the retina or LGN), because the clustering of points in this parameter space may indicate an underlying organizational principle. This paper concentrates on circular Gaussians, but the results generalize to multidimensional radially symmetric Gaussians and are given as an appendix.

Information theoretic methods for image processing algorithm optimization

NASA Astrophysics Data System (ADS)

Prokushkin, Sergey F.; Galil, Erez

2015-01-01

Modern image processing pipelines (e.g., those used in digital cameras) are full of advanced, highly adaptive filters that often have a large number of tunable parameters (sometimes > 100). This makes the calibration procedure for these filters very complex, and the optimal results barely achievable in the manual calibration; thus an automated approach is a must. We will discuss an information theory based metric for evaluation of algorithm adaptive characteristics ("adaptivity criterion") using noise reduction algorithms as an example. The method allows finding an "orthogonal decomposition" of the filter parameter space into the "filter adaptivity" and "filter strength" directions. This metric can be used as a cost function in automatic filter optimization. Since it is a measure of a physical "information restoration" rather than perceived image quality, it helps to reduce the set of the filter parameters to a smaller subset that is easier for a human operator to tune and achieve a better subjective image quality. With appropriate adjustments, the criterion can be used for assessment of the whole imaging system (sensor plus post-processing).

Study on High Speed Lithium Jet For Neutron Source of Boron Neutron Capture Therapy (BNCT)

NASA Astrophysics Data System (ADS)

Takahashi, Minoru; Kobayashi, Tooru; Zhang, Mingguang; Mák, Michael; Štefanica, Jirí; Dostál, Václav; Zhao, Wei

The feasibility study of a liquid lithium type proton beam target was performed for the neutron source of the boron neutron capture therapy (BNCT). As the candidates of the liquid lithium target, a thin sheet jet and a thin film flow on a concave wall were chosen, and a lithium flow experiment was conducted to investigate the hydrodynamic stability of the targets. The surfaces of the jets and film flows with a thickness of 0.5 mm and a width of 50 mm were observed by means of photography. It has been found that a stable sheet jet and a stable film flow on a concave wall can be formed up to certain velocities by using a straight nozzle and a curved nozzle with the concave wall, respectively.

Neutron collimator design of neutron radiography based on the BNCT facility

NASA Astrophysics Data System (ADS)

Yang, Xiao-Peng; Yu, Bo-Xiang; Li, Yi-Guo; Peng, Dan; Lu, Jin; Zhang, Gao-Long; Zhao, Hang; Zhang, Ai-Wu; Li, Chun-Yang; Liu, Wan-Jin; Hu, Tao; Lü, Jun-Guang

2014-02-01

For the research of CCD neutron radiography, a neutron collimator was designed based on the exit of thermal neutron of the Boron Neutron Capture Therapy (BNCT) reactor. Based on the Geant4 simulations, the preliminary choice of the size of the collimator was determined. The materials were selected according to the literature data. Then, a collimator was constructed and tested on site. The results of experiment and simulation show that the thermal neutron flux at the end of the neutron collimator is greater than 1.0×106 n/cm2/s, the maximum collimation ratio (L/D) is 58, the Cd-ratio(Mn) is 160 and the diameter of collimator end is 10 cm. This neutron collimator is considered to be applicable for neutron radiography.

Accelerator-driven boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Edgecock, Rob

2014-05-01

Boron Neutron Capture Therapy is a binary treatment for certain types of cancer. It works by loading the cancerous cells with a boron-10 carrying compound. This isotope has a large cross-section for thermal neutrons, the reaction producing a lithium nucleus and alpha particle that kill the cell in which they are produced. Recent studies of the boron carrier compound indicate that the uptake process works best in particularly aggressive cancers. Most studied is glioblastoma multiforme and a trial using a combination of BNCT and X-ray radiotherapy has shown an increase of nearly a factor of two in mean survival over the state of the art. However, the main technical problem with BNCT remains producing a sufficient flux of neutrons for a reasonable treatment duration in a hospital environment. This paper discusses this issue.

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments

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

Miller, Marcelo E.; Sztejnberg, Manuel L.; Gonzalez, Sara J.

2011-12-15

Purpose: A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comision Nacional de Energia Atomica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. Methods: The first calibration of the detector was done with themore » well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Results: Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 {+-} 0.05 x 10{sup -21} A n{sup -1}{center_dot}cm{sup 2}{center_dot}s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. Conclusions: The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.« less

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments.

PubMed

Miller, Marcelo E; Sztejnberg, Manuel L; González, Sara J; Thorp, Silvia I; Longhino, Juan M; Estryk, Guillermo

2011-12-01

A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comisión Nacional de Energía Atómica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 ± 0.05 × 10(-21) A n(-1)[middle dot]cm² [middle dot]s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.

Optimally designed narrowband guided-mode resonance reflectance filters for mid-infrared spectroscopy

PubMed Central

Liu, Jui-Nung; Schulmerich, Matthew V.; Bhargava, Rohit; Cunningham, Brian T.

2011-01-01

An alternative to the well-established Fourier transform infrared (FT-IR) spectrometry, termed discrete frequency infrared (DFIR) spectrometry, has recently been proposed. This approach uses narrowband mid-infrared reflectance filters based on guided-mode resonance (GMR) in waveguide gratings, but filters designed and fabricated have not attained the spectral selectivity (≤ 32 cm−1) commonly employed for measurements of condensed matter using FT-IR spectroscopy. With the incorporation of dispersion and optical absorption of materials, we present here optimal design of double-layer surface-relief silicon nitride-based GMR filters in the mid-IR for various narrow bandwidths below 32 cm−1. Both shift of the filter resonance wavelengths arising from the dispersion effect and reduction of peak reflection efficiency and electric field enhancement due to the absorption effect show that the optical characteristics of materials must be taken into consideration rigorously for accurate design of narrowband GMR filters. By incorporating considerations for background reflections, the optimally designed GMR filters can have bandwidth narrower than the designed filter by the antireflection equivalence method based on the same index modulation magnitude, without sacrificing low sideband reflections near resonance. The reported work will enable use of GMR filters-based instrumentation for common measurements of condensed matter, including tissues and polymer samples. PMID:22109445

CONVECTION ENHANCED DELIVERY OF CARBORANYLPORPHYRINS FOR NEUTRON CAPTURE THERAPY OF BRAIN TUMORS

PubMed Central

Kawabata, Shinji; Yang, Weilian; Wu, Gong; Huo, Tianyao; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, M. Graça H.

2010-01-01

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α]7Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these have been evaluated in the present study: 5,10,15,20-tetra-(4-nido-carboranyphenyl)tetrabenzoporphyrin (H2TBP), 5,10,15,20-tetra-(4-nido-carboranylphenyl)porphyrin (H2TCP) and 5,15-di-[3,5-(nido-carboranylmethyl)phenyl]-porphyrin (H2DCP). The goals of this study were two-fold. First, to determine the biodistribution of H2TBP, H2TCP and H2DCP following intracerebral (i.c.) administration by means of short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. osmotic pump delivery were high (36–88 µg/g) and they remained so at 24 h (62–103 µg/g) The corresponding normal brain concentrations were low (0.8–5.2 µg/g) and the blood and liver concentrations were all undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) with H2TCP and H2TBP 24 h after CED or osmotic pump delivery. Mean survival times (MST) of untreated and irradiated control rats were 23±3 and 27±3 d, respectively, while animals that received H2TCP or H2TBP, followed by BNCT, had a MST of 35±4 d and 44±10 d, respectively, which were better than those obtained following i.v. administration of boronophenylalanine (37±3 d). However, since the tumor boron concentrations of the carboranylporphyrins were 3–5X > i.v. BPA (~25 µg/g), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed that there were large numbers of porphyrin-laden macrophages, as well as extracellular accumulations of porphyrins indicating that the seemingly high tumor boron concentrations did not represent the true tumor cellular uptake. Our data are the first to show that carboranyl porphyrins are effective delivery agents for BNCT of an experimental brain tumor. Based on these results, we now are in the process of evaluating carboranylporphyrins that could have enhanced cellular uptake following administration and improved therapeutic efficacy. PMID:20848301

Phase Response Design of Recursive All-Pass Digital Filters Using a Modified PSO Algorithm

PubMed Central

2015-01-01

This paper develops a new design scheme for the phase response of an all-pass recursive digital filter. A variant of particle swarm optimization (PSO) algorithm will be utilized for solving this kind of filter design problem. It is here called the modified PSO (MPSO) algorithm in which another adjusting factor is more introduced in the velocity updating formula of the algorithm in order to improve the searching ability. In the proposed method, all of the designed filter coefficients are firstly collected to be a parameter vector and this vector is regarded as a particle of the algorithm. The MPSO with a modified velocity formula will force all particles into moving toward the optimal or near optimal solution by minimizing some defined objective function of the optimization problem. To show the effectiveness of the proposed method, two different kinds of linear phase response design examples are illustrated and the general PSO algorithm is compared as well. The obtained results show that the MPSO is superior to the general PSO for the phase response design of digital recursive all-pass filter. PMID:26366168

Optimization Algorithm for Kalman Filter Exploiting the Numerical Characteristics of SINS/GPS Integrated Navigation Systems.

PubMed

Hu, Shaoxing; Xu, Shike; Wang, Duhu; Zhang, Aiwu

2015-11-11

Aiming at addressing the problem of high computational cost of the traditional Kalman filter in SINS/GPS, a practical optimization algorithm with offline-derivation and parallel processing methods based on the numerical characteristics of the system is presented in this paper. The algorithm exploits the sparseness and/or symmetry of matrices to simplify the computational procedure. Thus plenty of invalid operations can be avoided by offline derivation using a block matrix technique. For enhanced efficiency, a new parallel computational mechanism is established by subdividing and restructuring calculation processes after analyzing the extracted "useful" data. As a result, the algorithm saves about 90% of the CPU processing time and 66% of the memory usage needed in a classical Kalman filter. Meanwhile, the method as a numerical approach needs no precise-loss transformation/approximation of system modules and the accuracy suffers little in comparison with the filter before computational optimization. Furthermore, since no complicated matrix theories are needed, the algorithm can be easily transplanted into other modified filters as a secondary optimization method to achieve further efficiency.

Cat Swarm Optimization algorithm for optimal linear phase FIR filter design.

PubMed

Saha, Suman Kumar; Ghoshal, Sakti Prasad; Kar, Rajib; Mandal, Durbadal

2013-11-01

In this paper a new meta-heuristic search method, called Cat Swarm Optimization (CSO) algorithm is applied to determine the best optimal impulse response coefficients of FIR low pass, high pass, band pass and band stop filters, trying to meet the respective ideal frequency response characteristics. CSO is generated by observing the behaviour of cats and composed of two sub-models. In CSO, one can decide how many cats are used in the iteration. Every cat has its' own position composed of M dimensions, velocities for each dimension, a fitness value which represents the accommodation of the cat to the fitness function, and a flag to identify whether the cat is in seeking mode or tracing mode. The final solution would be the best position of one of the cats. CSO keeps the best solution until it reaches the end of the iteration. The results of the proposed CSO based approach have been compared to those of other well-known optimization methods such as Real Coded Genetic Algorithm (RGA), standard Particle Swarm Optimization (PSO) and Differential Evolution (DE). The CSO based results confirm the superiority of the proposed CSO for solving FIR filter design problems. The performances of the CSO based designed FIR filters have proven to be superior as compared to those obtained by RGA, conventional PSO and DE. The simulation results also demonstrate that the CSO is the best optimizer among other relevant techniques, not only in the convergence speed but also in the optimal performances of the designed filters. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Assessment of intermittently loaded woodchip and sand filters to treat dairy soiled water.

PubMed

Murnane, J G; Brennan, R B; Healy, M G; Fenton, O

2016-10-15

Land application of dairy soiled water (DSW) is expensive relative to its nutrient replacement value. The use of aerobic filters is an effective alternative method of treatment and potentially allows the final effluent to be reused on the farm. Knowledge gaps exist concerning the optimal design and operation of filters for the treatment of DSW. To address this, 18 laboratory-scale filters, with depths of either 0.6 m or 1 m, were intermittently loaded with DSW over periods of up to 220 days to evaluate the impacts of depth (0.6 m versus 1 m), organic loading rates (OLRs) (50 versus 155 g COD m(-2) d(-1)), and media type (woodchip versus sand) on organic, nutrient and suspended solids (SS) removals. The study found that media depth was important in contaminant removal in woodchip filters. Reductions of 78% chemical oxygen demand (COD), 95% SS, 85% total nitrogen (TN), 82% ammonium-nitrogen (NH4N), 50% total phosphorus (TP), and 54% dissolved reactive phosphorus (DRP) were measured in 1 m deep woodchip filters, which was greater than the reductions in 0.6 m deep woodchip filters. Woodchip filters also performed optimally when loaded at a high OLR (155 g COD m(-2) d(-1)), although the removal mechanism was primarily physical (i.e. straining) as opposed to biological. When operated at the same OLR and when of the same depth, the sand filters had better COD removals (96%) than woodchip (74%), but there was no significant difference between them in the removal of SS and NH4N. However, the likelihood of clogging makes sand filters less desirable than woodchip filters. Using the optimal designs of both configurations, the filter area required per cow for a woodchip filter is more than four times less than for a sand filter. Therefore, this study found that woodchip filters are more economically and environmentally effective in the treatment of DSW than sand filters, and optimal performance may be achieved using woodchip filters with a depth of at least 1 m, operated at an OLR of 155 g COD m(-2) d(-1). Copyright © 2016 Elsevier Ltd. All rights reserved.

Performance evaluation of an asynchronous multisensor track fusion filter

NASA Astrophysics Data System (ADS)

Alouani, Ali T.; Gray, John E.; McCabe, D. H.

2003-08-01

Recently the authors developed a new filter that uses data generated by asynchronous sensors to produce a state estimate that is optimal in the minimum mean square sense. The solution accounts for communications delay between sensors platform and fusion center. It also deals with out of sequence data as well as latent data by processing the information in a batch-like manner. This paper compares, using simulated targets and Monte Carlo simulations, the performance of the filter to the optimal sequential processing approach. It was found that the new asynchronous Multisensor track fusion filter (AMSTFF) performance is identical to that of the extended sequential Kalman filter (SEKF), while the new filter updates its track at a much lower rate than the SEKF.

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

PubMed

Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Lin, Ko-Han; Wang, Shyh-Jen; Chu, Pen-Yuan; Lo, Wen-Liang; Kao, Shou-Yen; Yen, Sang-Hue

2016-05-01

To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

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

Carpano, Marina; Perona, Marina; Rodriguez, Carla

Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a speciallymore » modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.« less

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial

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

Wang, Ling-Wei, E-mail: lwwang@vghtpe.gov.tw; National Yang-Ming University, Taiwan; Chen, Yi-Wei

Purpose: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. Methods and Materials: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA–positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq.more » Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Results: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Conclusions: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.« less

Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.

PubMed

Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra

2015-10-01

Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit). We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion. Copyright © 2015 Elsevier Inc. All rights reserved.

Event-triggered resilient filtering with stochastic uncertainties and successive packet dropouts via variance-constrained approach

NASA Astrophysics Data System (ADS)

Jia, Chaoqing; Hu, Jun; Chen, Dongyan; Liu, Yurong; Alsaadi, Fuad E.

2018-07-01

In this paper, we discuss the event-triggered resilient filtering problem for a class of time-varying systems subject to stochastic uncertainties and successive packet dropouts. The event-triggered mechanism is employed with hope to reduce the communication burden and save network resources. The stochastic uncertainties are considered to describe the modelling errors and the phenomenon of successive packet dropouts is characterized by a random variable obeying the Bernoulli distribution. The aim of the paper is to provide a resilient event-based filtering approach for addressed time-varying systems such that, for all stochastic uncertainties, successive packet dropouts and filter gain perturbation, an optimized upper bound of the filtering error covariance is obtained by designing the filter gain. Finally, simulations are provided to demonstrate the effectiveness of the proposed robust optimal filtering strategy.

Optimal Sharpening of Compensated Comb Decimation Filters: Analysis and Design

PubMed Central

Troncoso Romero, David Ernesto

2014-01-01

Comb filters are a class of low-complexity filters especially useful for multistage decimation processes. However, the magnitude response of comb filters presents a droop in the passband region and low stopband attenuation, which is undesirable in many applications. In this work, it is shown that, for stringent magnitude specifications, sharpening compensated comb filters requires a lower-degree sharpening polynomial compared to sharpening comb filters without compensation, resulting in a solution with lower computational complexity. Using a simple three-addition compensator and an optimization-based derivation of sharpening polynomials, we introduce an effective low-complexity filtering scheme. Design examples are presented in order to show the performance improvement in terms of passband distortion and selectivity compared to other methods based on the traditional Kaiser-Hamming sharpening and the Chebyshev sharpening techniques recently introduced in the literature. PMID:24578674

Optimal sharpening of compensated comb decimation filters: analysis and design.

PubMed

Troncoso Romero, David Ernesto; Laddomada, Massimiliano; Jovanovic Dolecek, Gordana

2014-01-01

Comb filters are a class of low-complexity filters especially useful for multistage decimation processes. However, the magnitude response of comb filters presents a droop in the passband region and low stopband attenuation, which is undesirable in many applications. In this work, it is shown that, for stringent magnitude specifications, sharpening compensated comb filters requires a lower-degree sharpening polynomial compared to sharpening comb filters without compensation, resulting in a solution with lower computational complexity. Using a simple three-addition compensator and an optimization-based derivation of sharpening polynomials, we introduce an effective low-complexity filtering scheme. Design examples are presented in order to show the performance improvement in terms of passband distortion and selectivity compared to other methods based on the traditional Kaiser-Hamming sharpening and the Chebyshev sharpening techniques recently introduced in the literature.

Optimal filter parameters for low SNR seismograms as a function of station and event location

NASA Astrophysics Data System (ADS)

Leach, Richard R.; Dowla, Farid U.; Schultz, Craig A.

1999-06-01

Global seismic monitoring requires deployment of seismic sensors worldwide, in many areas that have not been studied or have few useable recordings. Using events with lower signal-to-noise ratios (SNR) would increase the amount of data from these regions. Lower SNR events can add significant numbers to data sets, but recordings of these events must be carefully filtered. For a given region, conventional methods of filter selection can be quite subjective and may require intensive analysis of many events. To reduce this laborious process, we have developed an automated method to provide optimal filters for low SNR regional or teleseismic events. As seismic signals are often localized in frequency and time with distinct time-frequency characteristics, our method is based on the decomposition of a time series into a set of subsignals, each representing a band with f/Δ f constant (constant Q). The SNR is calculated on the pre-event noise and signal window. The band pass signals with high SNR are used to indicate the cutoff filter limits for the optimized filter. Results indicate a significant improvement in SNR, particularly for low SNR events. The method provides an optimum filter which can be immediately applied to unknown regions. The filtered signals are used to map the seismic frequency response of a region and may provide improvements in travel-time picking, azimuth estimation, regional characterization, and event detection. For example, when an event is detected and a preliminary location is determined, the computer could automatically select optimal filter bands for data from non-reporting stations. Results are shown for a set of low SNR events as well as 379 regional and teleseismic events recorded at stations ABKT, KIV, and ANTO in the Middle East.

Renovation of epithermal neutron beam for BNCT at THOR.

PubMed

Liu, Y-W H; Huang, T T; Jiang, S H; Liu, H M

2004-11-01

Heading for possible use for clinical trial, THOR (Tsing Hua Open-pool Reactor) at Taiwan was shutdown for renovation of a new epithermal neutron beam in January 2003. In November 2003, concrete cutting was finished for closer distance from core and larger treatment room. This article presents the design base that the construction of the new beam is based on. The filter/moderator design along the beam is Cd(0.1cm)+Al(10 cm)+FLUENTAL (16 cm)+Al(10 cm)+FLUENTAL(24 cm)+Void(18 cm)+Cd(0.1cm)+Bi(10 cm) with 6 cm Pb as reflector. Following the filter/moderator is an 88 cm long, 6 cm thick Bi-lined collimator with Li(2)CO(3)-PE at the end. The collimator is surrounded by Li(2)CO(3)-PE and Pb. The calculated beam parameters under 2 MW at the beam exit is phi(epi) = 3.4 x 10(9) n/cm(2)/s, Df/phi(epi) = 2.8 x 10(-11) cGy cm(2)/n, Dgamma/phi(epi) = 1.3 x 10(-11) cGy cm(2)/n, and J+/phi = 0.8. For a phantom placed 10 cm from beam exit, MCNP calculation shows that the advantage depth is 8.9 cm, and advantage ratio is 5.6 if boron concentration in tumor and normal tissue are assumed to be 65 and 18 ppm. The maximum dose rate for normal tissue is 50 cGy/min. The maximum therapeutic ratio is 6. The construction of the beam is scheduled to be finished by the end of April 2004.

Optimal Recursive Digital Filters for Active Bending Stabilization

NASA Technical Reports Server (NTRS)

Orr, Jeb S.

2013-01-01

In the design of flight control systems for large flexible boosters, it is common practice to utilize active feedback control of the first lateral structural bending mode so as to suppress transients and reduce gust loading. Typically, active stabilization or phase stabilization is achieved by carefully shaping the loop transfer function in the frequency domain via the use of compensating filters combined with the frequency response characteristics of the nozzle/actuator system. In this paper we present a new approach for parameterizing and determining optimal low-order recursive linear digital filters so as to satisfy phase shaping constraints for bending and sloshing dynamics while simultaneously maximizing attenuation in other frequency bands of interest, e.g. near higher frequency parasitic structural modes. By parameterizing the filter directly in the z-plane with certain restrictions, the search space of candidate filter designs that satisfy the constraints is restricted to stable, minimum phase recursive low-pass filters with well-conditioned coefficients. Combined with optimal output feedback blending from multiple rate gyros, the present approach enables rapid and robust parametrization of autopilot bending filters to attain flight control performance objectives. Numerical results are presented that illustrate the application of the present technique to the development of rate gyro filters for an exploration-class multi-engined space launch vehicle.

Kalman Filter Constraint Tuning for Turbofan Engine Health Estimation

NASA Technical Reports Server (NTRS)

Simon, Dan; Simon, Donald L.

2005-01-01

Kalman filters are often used to estimate the state variables of a dynamic system. However, in the application of Kalman filters some known signal information is often either ignored or dealt with heuristically. For instance, state variable constraints are often neglected because they do not fit easily into the structure of the Kalman filter. Recently published work has shown a new method for incorporating state variable inequality constraints in the Kalman filter, which has been shown to generally improve the filter s estimation accuracy. However, the incorporation of inequality constraints poses some risk to the estimation accuracy as the Kalman filter is theoretically optimal. This paper proposes a way to tune the filter constraints so that the state estimates follow the unconstrained (theoretically optimal) filter when the confidence in the unconstrained filter is high. When confidence in the unconstrained filter is not so high, then we use our heuristic knowledge to constrain the state estimates. The confidence measure is based on the agreement of measurement residuals with their theoretical values. The algorithm is demonstrated on a linearized simulation of a turbofan engine to estimate engine health.

Adapted all-numerical correlator for face recognition applications

NASA Astrophysics Data System (ADS)

Elbouz, M.; Bouzidi, F.; Alfalou, A.; Brosseau, C.; Leonard, I.; Benkelfat, B.-E.

2013-03-01

In this study, we suggest and validate an all-numerical implementation of a VanderLugt correlator which is optimized for face recognition applications. The main goal of this implementation is to take advantage of the benefits (detection, localization, and identification of a target object within a scene) of correlation methods and exploit the reconfigurability of numerical approaches. This technique requires a numerical implementation of the optical Fourier transform. We pay special attention to adapt the correlation filter to this numerical implementation. One main goal of this work is to reduce the size of the filter in order to decrease the memory space required for real time applications. To fulfil this requirement, we code the reference images with 8 bits and study the effect of this coding on the performances of several composite filters (phase-only filter, binary phase-only filter). The saturation effect has for effect to decrease the performances of the correlator for making a decision when filters contain up to nine references. Further, an optimization is proposed based for an optimized segmented composite filter. Based on this approach, we present tests with different faces demonstrating that the above mentioned saturation effect is significantly reduced while minimizing the size of the learning data base.

Multiple local feature representations and their fusion based on an SVR model for iris recognition using optimized Gabor filters

NASA Astrophysics Data System (ADS)

He, Fei; Liu, Yuanning; Zhu, Xiaodong; Huang, Chun; Han, Ye; Dong, Hongxing

2014-12-01

Gabor descriptors have been widely used in iris texture representations. However, fixed basic Gabor functions cannot match the changing nature of diverse iris datasets. Furthermore, a single form of iris feature cannot overcome difficulties in iris recognition, such as illumination variations, environmental conditions, and device variations. This paper provides multiple local feature representations and their fusion scheme based on a support vector regression (SVR) model for iris recognition using optimized Gabor filters. In our iris system, a particle swarm optimization (PSO)- and a Boolean particle swarm optimization (BPSO)-based algorithm is proposed to provide suitable Gabor filters for each involved test dataset without predefinition or manual modulation. Several comparative experiments on JLUBR-IRIS, CASIA-I, and CASIA-V4-Interval iris datasets are conducted, and the results show that our work can generate improved local Gabor features by using optimized Gabor filters for each dataset. In addition, our SVR fusion strategy may make full use of their discriminative ability to improve accuracy and reliability. Other comparative experiments show that our approach may outperform other popular iris systems.

Robotic fish tracking method based on suboptimal interval Kalman filter

NASA Astrophysics Data System (ADS)

Tong, Xiaohong; Tang, Chao

2017-11-01

Autonomous Underwater Vehicle (AUV) research focused on tracking and positioning, precise guidance and return to dock and other fields. The robotic fish of AUV has become a hot application in intelligent education, civil and military etc. In nonlinear tracking analysis of robotic fish, which was found that the interval Kalman filter algorithm contains all possible filter results, but the range is wide, relatively conservative, and the interval data vector is uncertain before implementation. This paper proposes a ptimization algorithm of suboptimal interval Kalman filter. Suboptimal interval Kalman filter scheme used the interval inverse matrix with its worst inverse instead, is more approximate nonlinear state equation and measurement equation than the standard interval Kalman filter, increases the accuracy of the nominal dynamic system model, improves the speed and precision of tracking system. Monte-Carlo simulation results show that the optimal trajectory of sub optimal interval Kalman filter algorithm is better than that of the interval Kalman filter method and the standard method of the filter.

Characteristics and application of spherical-type activation detectors in neutron spectrum measurements at a boron neutron capture therapy (BNCT) facility

NASA Astrophysics Data System (ADS)

Lin, Heng-Xiao; Chen, Wei-Lin; Liu, Yuan-Hao; Sheu, Rong-Jiun

2016-03-01

A set of spherical-type activation detectors was developed aiming to provide better determination of the neutron spectrum at the Tsing Hua Open-pool Reactor (THOR) BNCT facility. An activation foil embedded in a specially designed spherical holder exhibits three advantages: (1) minimizing the effect of neutron angular dependence, (2) creating response functions with broadened coverage of neutron energies by introducing additional moderators or absorbers to the central activation foil, and (3) reducing irradiation time because of improved detection efficiencies to epithermal neutron beam. This paper presents the design concept and the calculated response functions of new detectors. Theoretical and experimental demonstrations of the performance of the detectors are provided through comparisons of the unfolded neutron spectra determined using this method and conventional multiple-foil activation techniques.

Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

PubMed

Kumada, Hiroaki; Kurihara, Toshikazu; Yoshioka, Masakazu; Kobayashi, Hitoshi; Matsumoto, Hiroshi; Sugano, Tomei; Sakurai, Hideyuki; Sakae, Takeji; Matsumura, Akira

2015-12-01

The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Monte Carlo based dosimetry for neutron capture therapy of brain tumors

NASA Astrophysics Data System (ADS)

Zaidi, Lilia; Belgaid, Mohamed; Khelifi, Rachid

2016-11-01

Boron Neutron Capture Therapy (BNCT) is a biologically targeted, radiation therapy for cancer which combines neutron irradiation with a tumor targeting agent labeled with a boron10 having a high thermal neutron capture cross section. The tumor area is subjected to the neutron irradiation. After a thermal neutron capture, the excited 11B nucleus fissions into an alpha particle and lithium recoil nucleus. The high Linear Energy Transfer (LET) emitted particles deposit their energy in a range of about 10μm, which is of the same order of cell diameter [1], at the same time other reactions due to neutron activation with body component are produced. In-phantom measurement of physical dose distribution is very important for BNCT planning validation. Determination of total absorbed dose requires complex calculations which were carried out using the Monte Carlo MCNP code [2].

Boron absorption imaging in rat lung colon adenocarcinoma metastases

NASA Astrophysics Data System (ADS)

Altieri, S.; Bortolussi, S.; Bruschi, P.; Fossati, F.; Vittor, K.; Nano, R.; Facoetti, A.; Chiari, P.; Bakeine, J.; Clerici, A.; Ferrari, C.; Salvucci, O.

2006-05-01

Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher 10B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of 10B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

PubMed

Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

2015-10-01

Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Assessment of the Potential Use of BNNTs for Boron Neutron Capture Therapy.

PubMed

Ferreira, Tiago H; Miranda, Marcelo C; Rocha, Zildete; Leal, Alexandre S; Gomes, Dawidson A; Sousa, Edesia M B

2017-04-12

Currently, nanostructured compounds have been standing out for their optical, mechanical, and chemical features and for the possibilities of manipulation and regulation of complex biological processes. One of these compounds is boron nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal stability along with high chemical inertia. Among biological applications, its biocompatibility, cellular uptake, and functionalization potential can be highlighted, in addition to its eased utilization due to its nanometric size and tumor cell internalization. When it comes to new forms of therapy, we can draw attention to boron neutron capture therapy (BNCT), an experimental radiotherapy characterized by a boron-10 isotope carrier inside the target and a thermal neutron beam focused on it. The activation of the boron-10 atom by a neutron generates a lithium atom, a gamma ray, and an alpha particle, which can be used to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10 carrier for BNCT and to demonstrate its potential. The nanomaterial was characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated with the neutron beam of a Triga reactor, and the apoptosis caused by the activation of the BNNTs was measured with a calcein AM/propidium iodide test. The results demonstrate that this nanomaterial is a promising candidate for cancer therapy through BNCT.

Hadron Therapy in Latin America

NASA Astrophysics Data System (ADS)

Kreiner, A. J.; Bergueiro, J.; Burlon, A. A.; Di Paolo, H.; Castell, W.; Thatar Vento, V.; Levinas, P.; Cartelli, D.; Kesque, J. M.; Valda, A. A.; Ilardo, J. C.; Baldo, M.; Erhardt, J.; Debray, M. E.; Somacal, H. R.; Minsky, D. M.; Estrada, L.; Hazarabedian, A.; Johann, F.; Suarez Sandin, J. C.; Igarzabal, M.; Huck, H.; Repetto, M.; Obligado, M.; Lell, J.; Padulo, J.; Herrera, M.; Gonzalez, S. R.; Capoulat, M. E.; Davidson, J.; Davidson, M.

2010-08-01

The use of proton and heavy ion beams for radiotherapy is a well established cancer treatment modality in the first world, which is becoming increasingly widespread, due to its clear advantages over conventional photon-based treatments. This strategy is suitable when the tumor is spatially well localized. Also the use of neutrons has tradition. Here Boron Neutron Capture Therapy (BNCT) stands out, though on a much smaller scale, being a promising alternative for tumors which are diffuse and infiltrating. On this sector, so far only nuclear reactors have been used as neutron sources. In this paper we briefly describe the situation in Latin America and in particular we discuss the present status of an ongoing project to develop a folded Tandem-ElectroStatic-Quadrupole (TESQ) accelerator for Accelerator-Based (AB)-Boron Neutron Capture Therapy (BNCT) at the Atomic Energy Commission of Argentina. The project goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the 7Li(p,n)7Be reaction. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams to perform BNCT for deep-seated tumors in less than an hour. The machine being currently designed and constructed is a folded TESQ with a terminal at 0.6 MV as a smaller scale prototype. Since the concept is modular the same structure will be used for the 1.2 MV final accelerator.

Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Santa Cruz, Gustavo A.; González, Sara J.; Dagrosa, Alejandra; Schwint, Amanda E.; Carpano, Marina; Trivillin, Verónica A.; Boggio, Esteban F.; Bertotti, José; Marín, Julio; Monti Hughes, Andrea; Molinari, Ana J.; Albero, Miguel

2011-05-01

Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

Optimization of the cleaning process on a pilot filtration setup for waste water treatment accompanied by flow visualization

NASA Astrophysics Data System (ADS)

Bílek, Petr; Hrůza, Jakub

2018-06-01

This paper deals with an optimization of the cleaning process on a liquid flat-sheet filter accompanied by visualization of the inlet side of a filter. The cleaning process has a crucial impact on the hydrodynamic properties of flat-sheet filters. Cleaning methods avoid depositing of particles on the filter surface and forming a filtration cake. Visualization significantly helps to optimize the cleaning methods, because it brings new overall view on the filtration process in time. The optical method, described in the article, enables to see flow behaviour in a thin laser sheet on the inlet side of a tested filter during the cleaning process. Visualization is a strong tool for investigation of the processes on filters in details and it is also possible to determine concentration of particles after an image analysis. The impact of air flow rate, inverse pressure drop and duration on the cleaning mechanism is investigated in the article. Images of the cleaning process are compared to the hydrodynamic data. The tests are carried out on a pilot filtration setup for waste water treatment.

Simultaneous learning and filtering without delusions: a Bayes-optimal combination of Predictive Inference and Adaptive Filtering.

PubMed

Kneissler, Jan; Drugowitsch, Jan; Friston, Karl; Butz, Martin V

2015-01-01

Predictive coding appears to be one of the fundamental working principles of brain processing. Amongst other aspects, brains often predict the sensory consequences of their own actions. Predictive coding resembles Kalman filtering, where incoming sensory information is filtered to produce prediction errors for subsequent adaptation and learning. However, to generate prediction errors given motor commands, a suitable temporal forward model is required to generate predictions. While in engineering applications, it is usually assumed that this forward model is known, the brain has to learn it. When filtering sensory input and learning from the residual signal in parallel, a fundamental problem arises: the system can enter a delusional loop when filtering the sensory information using an overly trusted forward model. In this case, learning stalls before accurate convergence because uncertainty about the forward model is not properly accommodated. We present a Bayes-optimal solution to this generic and pernicious problem for the case of linear forward models, which we call Predictive Inference and Adaptive Filtering (PIAF). PIAF filters incoming sensory information and learns the forward model simultaneously. We show that PIAF is formally related to Kalman filtering and to the Recursive Least Squares linear approximation method, but combines these procedures in a Bayes optimal fashion. Numerical evaluations confirm that the delusional loop is precluded and that the learning of the forward model is more than 10-times faster when compared to a naive combination of Kalman filtering and Recursive Least Squares.

Optimal Design of Passive Power Filters Based on Pseudo-parallel Genetic Algorithm

NASA Astrophysics Data System (ADS)

Li, Pei; Li, Hongbo; Gao, Nannan; Niu, Lin; Guo, Liangfeng; Pei, Ying; Zhang, Yanyan; Xu, Minmin; Chen, Kerui

2017-05-01

The economic costs together with filter efficiency are taken as targets to optimize the parameter of passive filter. Furthermore, the method of combining pseudo-parallel genetic algorithm with adaptive genetic algorithm is adopted in this paper. In the early stages pseudo-parallel genetic algorithm is introduced to increase the population diversity, and adaptive genetic algorithm is used in the late stages to reduce the workload. At the same time, the migration rate of pseudo-parallel genetic algorithm is improved to change with population diversity adaptively. Simulation results show that the filter designed by the proposed method has better filtering effect with lower economic cost, and can be used in engineering.

Simplification of the Kalman filter for meteorological data assimilation

NASA Technical Reports Server (NTRS)

Dee, Dick P.

1991-01-01

The paper proposes a new statistical method of data assimilation that is based on a simplification of the Kalman filter equations. The forecast error covariance evolution is approximated simply by advecting the mass-error covariance field, deriving the remaining covariances geostrophically, and accounting for external model-error forcing only at the end of each forecast cycle. This greatly reduces the cost of computation of the forecast error covariance. In simulations with a linear, one-dimensional shallow-water model and data generated artificially, the performance of the simplified filter is compared with that of the Kalman filter and the optimal interpolation (OI) method. The simplified filter produces analyses that are nearly optimal, and represents a significant improvement over OI.

Identifying Optimal Measurement Subspace for the Ensemble Kalman Filter

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

Zhou, Ning; Huang, Zhenyu; Welch, Greg

2012-05-24

To reduce the computational load of the ensemble Kalman filter while maintaining its efficacy, an optimization algorithm based on the generalized eigenvalue decomposition method is proposed for identifying the most informative measurement subspace. When the number of measurements is large, the proposed algorithm can be used to make an effective tradeoff between computational complexity and estimation accuracy. This algorithm also can be extended to other Kalman filters for measurement subspace selection.

Learning-based 3D surface optimization from medical image reconstruction

NASA Astrophysics Data System (ADS)

Wei, Mingqiang; Wang, Jun; Guo, Xianglin; Wu, Huisi; Xie, Haoran; Wang, Fu Lee; Qin, Jing

2018-04-01

Mesh optimization has been studied from the graphical point of view: It often focuses on 3D surfaces obtained by optical and laser scanners. This is despite the fact that isosurfaced meshes of medical image reconstruction suffer from both staircases and noise: Isotropic filters lead to shape distortion, while anisotropic ones maintain pseudo-features. We present a data-driven method for automatically removing these medical artifacts while not introducing additional ones. We consider mesh optimization as a combination of vertex filtering and facet filtering in two stages: Offline training and runtime optimization. In specific, we first detect staircases based on the scanning direction of CT/MRI scanners, and design a staircase-sensitive Laplacian filter (vertex-based) to remove them; and then design a unilateral filtered facet normal descriptor (uFND) for measuring the geometry features around each facet of a given mesh, and learn the regression functions from a set of medical meshes and their high-resolution reference counterparts for mapping the uFNDs to the facet normals of the reference meshes (facet-based). At runtime, we first perform staircase-sensitive Laplacian filter on an input MC (Marching Cubes) mesh, and then filter the mesh facet normal field using the learned regression functions, and finally deform it to match the new normal field for obtaining a compact approximation of the high-resolution reference model. Tests show that our algorithm achieves higher quality results than previous approaches regarding surface smoothness and surface accuracy.

Performance Limits of Non-Line-of-Sight Optical Communications

DTIC Science & Technology

2015-05-01

high efficiency solar blind photo detectors. In this project, we address the main challenges towards optimizing the UV communication system...LEDs), solar blind filters, and high efficiency solar blind photo detectors. In this project, we address the main challenges towards optimizing the UV...solar blind filters, and high efficiency solar blind photo detectors. In this project, we address the main challenges towards optimizing the UV

On the ``optimal'' spatial distribution and directional anisotropy of the filter-width and grid-resolution in large eddy simulation

NASA Astrophysics Data System (ADS)

Toosi, Siavash; Larsson, Johan

2017-11-01

The accuracy of an LES depends directly on the accuracy of the resolved part of the turbulence. The continuing increase in computational power enables the application of LES to increasingly complex flow problems for which the LES community lacks the experience of knowing what the ``optimal'' or even an ``acceptable'' grid (or equivalently filter-width distribution) is. The goal of this work is to introduce a systematic approach to finding the ``optimal'' grid/filter-width distribution and their ``optimal'' anisotropy. The method is tested first on the turbulent channel flow, mainly to see if it is able to predict the right anisotropy of the filter/grid, and then on the more complicated case of flow over a backward-facing step, to test its ability to predict the right distribution and anisotropy of the filter/grid simultaneously, hence leading to a converged solution. This work has been supported by the Naval Air Warfare Center Aircraft Division at Pax River, MD, under contract N00421132M021. Computing time has been provided by the University of Maryland supercomputing resources (http://hpcc.umd.edu).

A comparison of optimal MIMO linear and nonlinear models for brain machine interfaces

NASA Astrophysics Data System (ADS)

Kim, S.-P.; Sanchez, J. C.; Rao, Y. N.; Erdogmus, D.; Carmena, J. M.; Lebedev, M. A.; Nicolelis, M. A. L.; Principe, J. C.

2006-06-01

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

A comparison of optimal MIMO linear and nonlinear models for brain-machine interfaces.

PubMed

Kim, S-P; Sanchez, J C; Rao, Y N; Erdogmus, D; Carmena, J M; Lebedev, M A; Nicolelis, M A L; Principe, J C

2006-06-01

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

Creation of an iOS and Android Mobile Application for Inferior Vena Cava (IVC) Filters: A Powerful Tool to Optimize Care of Patients with IVC Filters

PubMed Central

Deso, Steven E.; Idakoji, Ibrahim A.; Muelly, Michael C.; Kuo, William T.

2016-01-01

Owing to a myriad of inferior vena cava (IVC) filter types and their potential complications, rapid and correct identification may be challenging when encountered on routine imaging. The authors aimed to develop an interactive mobile application that allows recognition of all IVC filters and related complications, to optimize the care of patients with indwelling IVC filters. The FDA Premarket Notification Database was queried from 1980 to 2014 to identify all IVC filter types in the United States. An electronic search was then performed on MEDLINE and the FDA MAUDE database to identify all reported complications associated with each device. High-resolution photos were taken of each filter type and corresponding computed tomographic and fluoroscopic images were obtained from an institutional review board–approved IVC filter registry. A wireframe and storyboard were created, and software was developed using HTML5/CSS compliant code. The software was deployed using PhoneGap (Adobe, San Jose, CA), and the prototype was tested and refined. Twenty-three IVC filter types were identified for inclusion. Safety data from FDA MAUDE and 72 relevant peer-reviewed studies were acquired, and complication rates for each filter type were highlighted in the application. Digital photos, fluoroscopic images, and CT DICOM files were seamlessly incorporated. All data were succinctly organized electronically, and the software was successfully deployed into Android (Google, Mountain View, CA) and iOS (Apple, Cupertino, CA) platforms. A powerful electronic mobile application was successfully created to allow rapid identification of all IVC filter types and related complications. This application may be used to optimize the care of patients with IVC filters. PMID:27247483

Creation of an iOS and Android Mobile Application for Inferior Vena Cava (IVC) Filters: A Powerful Tool to Optimize Care of Patients with IVC Filters.

PubMed

Deso, Steven E; Idakoji, Ibrahim A; Muelly, Michael C; Kuo, William T

2016-06-01

Owing to a myriad of inferior vena cava (IVC) filter types and their potential complications, rapid and correct identification may be challenging when encountered on routine imaging. The authors aimed to develop an interactive mobile application that allows recognition of all IVC filters and related complications, to optimize the care of patients with indwelling IVC filters. The FDA Premarket Notification Database was queried from 1980 to 2014 to identify all IVC filter types in the United States. An electronic search was then performed on MEDLINE and the FDA MAUDE database to identify all reported complications associated with each device. High-resolution photos were taken of each filter type and corresponding computed tomographic and fluoroscopic images were obtained from an institutional review board-approved IVC filter registry. A wireframe and storyboard were created, and software was developed using HTML5/CSS compliant code. The software was deployed using PhoneGap (Adobe, San Jose, CA), and the prototype was tested and refined. Twenty-three IVC filter types were identified for inclusion. Safety data from FDA MAUDE and 72 relevant peer-reviewed studies were acquired, and complication rates for each filter type were highlighted in the application. Digital photos, fluoroscopic images, and CT DICOM files were seamlessly incorporated. All data were succinctly organized electronically, and the software was successfully deployed into Android (Google, Mountain View, CA) and iOS (Apple, Cupertino, CA) platforms. A powerful electronic mobile application was successfully created to allow rapid identification of all IVC filter types and related complications. This application may be used to optimize the care of patients with IVC filters.

Optimal-adaptive filters for modelling spectral shape, site amplification, and source scaling

USGS Publications Warehouse

Safak, Erdal

1989-01-01

This paper introduces some applications of optimal filtering techniques to earthquake engineering by using the so-called ARMAX models. Three applications are presented: (a) spectral modelling of ground accelerations, (b) site amplification (i.e., the relationship between two records obtained at different sites during an earthquake), and (c) source scaling (i.e., the relationship between two records obtained at a site during two different earthquakes). A numerical example for each application is presented by using recorded ground motions. The results show that the optimal filtering techniques provide elegant solutions to above problems, and can be a useful tool in earthquake engineering.

Optimal Weights Mixed Filter for removing mixture of Gaussian and impulse noises

PubMed Central

Grama, Ion; Liu, Quansheng

2017-01-01

In this paper we consider the problem of restoration of a image contaminated by a mixture of Gaussian and impulse noises. We propose a new statistic called ROADGI which improves the well-known Rank-Ordered Absolute Differences (ROAD) statistic for detecting points contaminated with the impulse noise in this context. Combining ROADGI statistic with the method of weights optimization we obtain a new algorithm called Optimal Weights Mixed Filter (OWMF) to deal with the mixed noise. Our simulation results show that the proposed filter is effective for mixed noises, as well as for single impulse noise and for single Gaussian noise. PMID:28692667

Optimal Weights Mixed Filter for removing mixture of Gaussian and impulse noises.

PubMed

Jin, Qiyu; Grama, Ion; Liu, Quansheng

2017-01-01

In this paper we consider the problem of restoration of a image contaminated by a mixture of Gaussian and impulse noises. We propose a new statistic called ROADGI which improves the well-known Rank-Ordered Absolute Differences (ROAD) statistic for detecting points contaminated with the impulse noise in this context. Combining ROADGI statistic with the method of weights optimization we obtain a new algorithm called Optimal Weights Mixed Filter (OWMF) to deal with the mixed noise. Our simulation results show that the proposed filter is effective for mixed noises, as well as for single impulse noise and for single Gaussian noise.

Combined adaptive multiple subtraction based on optimized event tracing and extended wiener filtering

NASA Astrophysics Data System (ADS)

Tan, Jun; Song, Peng; Li, Jinshan; Wang, Lei; Zhong, Mengxuan; Zhang, Xiaobo

2017-06-01

The surface-related multiple elimination (SRME) method is based on feedback formulation and has become one of the most preferred multiple suppression methods used. However, some differences are apparent between the predicted multiples and those in the source seismic records, which may result in conventional adaptive multiple subtraction methods being barely able to effectively suppress multiples in actual production. This paper introduces a combined adaptive multiple attenuation method based on the optimized event tracing technique and extended Wiener filtering. The method firstly uses multiple records predicted by SRME to generate a multiple velocity spectrum, then separates the original record to an approximate primary record and an approximate multiple record by applying the optimized event tracing method and short-time window FK filtering method. After applying the extended Wiener filtering method, residual multiples in the approximate primary record can then be eliminated and the damaged primary can be restored from the approximate multiple record. This method combines the advantages of multiple elimination based on the optimized event tracing method and the extended Wiener filtering technique. It is an ideal method for suppressing typical hyperbolic and other types of multiples, with the advantage of minimizing damage of the primary. Synthetic and field data tests show that this method produces better multiple elimination results than the traditional multi-channel Wiener filter method and is more suitable for multiple elimination in complicated geological areas.

Comparison of cryogenic low-pass filters.

PubMed

Thalmann, M; Pernau, H-F; Strunk, C; Scheer, E; Pietsch, T

2017-11-01

Low-temperature electronic transport measurements with high energy resolution require both effective low-pass filtering of high-frequency input noise and an optimized thermalization of the electronic system of the experiment. In recent years, elaborate filter designs have been developed for cryogenic low-level measurements, driven by the growing interest in fundamental quantum-physical phenomena at energy scales corresponding to temperatures in the few millikelvin regime. However, a single filter concept is often insufficient to thermalize the electronic system to the cryogenic bath and eliminate spurious high frequency noise. Moreover, the available concepts often provide inadequate filtering to operate at temperatures below 10 mK, which are routinely available now in dilution cryogenic systems. Herein we provide a comprehensive analysis of commonly used filter types, introduce a novel compact filter type based on ferrite compounds optimized for the frequency range above 20 GHz, and develop an improved filtering scheme providing adaptable broad-band low-pass characteristic for cryogenic low-level and quantum measurement applications at temperatures down to few millikelvin.

Comparison of cryogenic low-pass filters

NASA Astrophysics Data System (ADS)

Thalmann, M.; Pernau, H.-F.; Strunk, C.; Scheer, E.; Pietsch, T.

2017-11-01

Low-temperature electronic transport measurements with high energy resolution require both effective low-pass filtering of high-frequency input noise and an optimized thermalization of the electronic system of the experiment. In recent years, elaborate filter designs have been developed for cryogenic low-level measurements, driven by the growing interest in fundamental quantum-physical phenomena at energy scales corresponding to temperatures in the few millikelvin regime. However, a single filter concept is often insufficient to thermalize the electronic system to the cryogenic bath and eliminate spurious high frequency noise. Moreover, the available concepts often provide inadequate filtering to operate at temperatures below 10 mK, which are routinely available now in dilution cryogenic systems. Herein we provide a comprehensive analysis of commonly used filter types, introduce a novel compact filter type based on ferrite compounds optimized for the frequency range above 20 GHz, and develop an improved filtering scheme providing adaptable broad-band low-pass characteristic for cryogenic low-level and quantum measurement applications at temperatures down to few millikelvin.

Optimal interpolation and the Kalman filter. [for analysis of numerical weather predictions

NASA Technical Reports Server (NTRS)

Cohn, S.; Isaacson, E.; Ghil, M.

1981-01-01

The estimation theory of stochastic-dynamic systems is described and used in a numerical study of optimal interpolation. The general form of data assimilation methods is reviewed. The Kalman-Bucy, KB filter, and optimal interpolation (OI) filters are examined for effectiveness in performance as gain matrices using a one-dimensional form of the shallow-water equations. Control runs in the numerical analyses were performed for a ten-day forecast in concert with the OI method. The effects of optimality, initialization, and assimilation were studied. It was found that correct initialization is necessary in order to localize errors, especially near boundary points. Also, the use of small forecast error growth rates over data-sparse areas was determined to offset inaccurate modeling of correlation functions near boundaries.

Ares-I Bending Filter Design using a Constrained Optimization Approach

NASA Technical Reports Server (NTRS)

Hall, Charles; Jang, Jiann-Woei; Hall, Robert; Bedrossian, Nazareth

2008-01-01

The Ares-I launch vehicle represents a challenging flex-body structural environment for control system design. Software filtering of the inertial sensor output is required to ensure adequate stable response to guidance commands while minimizing trajectory deviations. This paper presents a design methodology employing numerical optimization to develop the Ares-I bending filters. The design objectives include attitude tracking accuracy and robust stability with respect to rigid body dynamics, propellant slosh, and flex. Under the assumption that the Ares-I time-varying dynamics and control system can be frozen over a short period of time, the bending filters are designed to stabilize all the selected frozen-time launch control systems in the presence of parameter uncertainty. To ensure adequate response to guidance command, step response specifications are introduced as constraints in the optimization problem. Imposing these constrains minimizes performance degradation caused by the addition of the bending filters. The first stage bending filter design achieves stability by adding lag to the first structural frequency to phase stabilize the first flex mode while gain stabilizing the higher modes. The upper stage bending filter design gain stabilizes all the flex bending modes. The bending filter designs provided here have been demonstrated to provide stable first and second stage control systems in both Draper Ares Stability Analysis Tool (ASAT) and the MSFC MAVERIC 6DOF nonlinear time domain simulation.

Optimal design of FIR triplet halfband filter bank and application in image coding.

PubMed

Kha, H H; Tuan, H D; Nguyen, T Q

2011-02-01

This correspondence proposes an efficient semidefinite programming (SDP) method for the design of a class of linear phase finite impulse response triplet halfband filter banks whose filters have optimal frequency selectivity for a prescribed regularity order. The design problem is formulated as the minimization of the least square error subject to peak error constraints and regularity constraints. By using the linear matrix inequality characterization of the trigonometric semi-infinite constraints, it can then be exactly cast as a SDP problem with a small number of variables and, hence, can be solved efficiently. Several design examples of the triplet halfband filter bank are provided for illustration and comparison with previous works. Finally, the image coding performance of the filter bank is presented.

Optimal design of active EMC filters

NASA Astrophysics Data System (ADS)

Chand, B.; Kut, T.; Dickmann, S.

2013-07-01

A recent trend in automotive industry is adding electrical drive systems to conventional drives. The electrification allows an expansion of energy sources and provides great opportunities for environmental friendly mobility. The electrical powertrain and its components can also cause disturbances which couple into nearby electronic control units and communication cables. Therefore the communication can be degraded or even permanently disrupted. To minimize these interferences, different approaches are possible. One possibility is to use EMC filters. However, the diversity of filters is very large and the determination of an appropriate filter for each application is time-consuming. Therefore, the filter design is determined by using a simulation tool including an effective optimization algorithm. This method leads to improvements in terms of weight, volume and cost.

Optimization of internet content filtering-Combined with KNN and OCAT algorithms

NASA Astrophysics Data System (ADS)

Guo, Tianze; Wu, Lingjing; Liu, Jiaming

2018-04-01

The face of the status quo that rampant illegal content in the Internet, the result of traditional way to filter information, keyword recognition and manual screening, is getting worse. Based on this, this paper uses OCAT algorithm nested by KNN classification algorithm to construct a corpus training library that can dynamically learn and update, which can be improved on the filter corpus for constantly updated illegal content of the network, including text and pictures, and thus can better filter and investigate illegal content and its source. After that, the research direction will focus on the simplified updating of recognition and comparison algorithms and the optimization of the corpus learning ability in order to improve the efficiency of filtering, save time and resources.

Desensitized Optimal Filtering and Sensor Fusion Toolkit

NASA Technical Reports Server (NTRS)

Karlgaard, Christopher D.

2015-01-01

Analytical Mechanics Associates, Inc., has developed a software toolkit that filters and processes navigational data from multiple sensor sources. A key component of the toolkit is a trajectory optimization technique that reduces the sensitivity of Kalman filters with respect to model parameter uncertainties. The sensor fusion toolkit also integrates recent advances in adaptive Kalman and sigma-point filters for non-Gaussian problems with error statistics. This Phase II effort provides new filtering and sensor fusion techniques in a convenient package that can be used as a stand-alone application for ground support and/or onboard use. Its modular architecture enables ready integration with existing tools. A suite of sensor models and noise distribution as well as Monte Carlo analysis capability are included to enable statistical performance evaluations.

Application of optimal control theory to the design of the NASA/JPL 70-meter antenna servos

NASA Technical Reports Server (NTRS)

Alvarez, L. S.; Nickerson, J.

1989-01-01

The application of Linear Quadratic Gaussian (LQG) techniques to the design of the 70-m axis servos is described. Linear quadratic optimal control and Kalman filter theory are reviewed, and model development and verification are discussed. Families of optimal controller and Kalman filter gain vectors were generated by varying weight parameters. Performance specifications were used to select final gain vectors.

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

PubMed Central

Morris, G M; Smith, D R; Patel, H; Chandra, S; Morrison, G H; Hopewell, J W; Rezvani, M; Micca, P L; Coderre, J A

2000-01-01

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 ± 0.02. This compares with a previously published CBE factor for BPA of 4.87 ± 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT. © 2000 Cancer Research Campaign PMID:10839288

Adaptive sparsest narrow-band decomposition method and its applications to rolling element bearing fault diagnosis

NASA Astrophysics Data System (ADS)

Cheng, Junsheng; Peng, Yanfeng; Yang, Yu; Wu, Zhantao

2017-02-01

Enlightened by ASTFA method, adaptive sparsest narrow-band decomposition (ASNBD) method is proposed in this paper. In ASNBD method, an optimized filter must be established at first. The parameters of the filter are determined by solving a nonlinear optimization problem. A regulated differential operator is used as the objective function so that each component is constrained to be a local narrow-band signal. Afterwards, the signal is filtered by the optimized filter to generate an intrinsic narrow-band component (INBC). ASNBD is proposed aiming at solving the problems existed in ASTFA. Gauss-Newton type method, which is applied to solve the optimization problem in ASTFA, is irreplaceable and very sensitive to initial values. However, more appropriate optimization method such as genetic algorithm (GA) can be utilized to solve the optimization problem in ASNBD. Meanwhile, compared with ASTFA, the decomposition results generated by ASNBD have better physical meaning by constraining the components to be local narrow-band signals. Comparisons are made between ASNBD, ASTFA and EMD by analyzing simulation and experimental signals. The results indicate that ASNBD method is superior to the other two methods in generating more accurate components from noise signal, restraining the boundary effect, possessing better orthogonality and diagnosing rolling element bearing fault.

Plate/shell structure topology optimization of orthotropic material for buckling problem based on independent continuous topological variables

NASA Astrophysics Data System (ADS)

Ye, Hong-Ling; Wang, Wei-Wei; Chen, Ning; Sui, Yun-Kang

2017-10-01

The purpose of the present work is to study the buckling problem with plate/shell topology optimization of orthotropic material. A model of buckling topology optimization is established based on the independent, continuous, and mapping method, which considers structural mass as objective and buckling critical loads as constraints. Firstly, composite exponential function (CEF) and power function (PF) as filter functions are introduced to recognize the element mass, the element stiffness matrix, and the element geometric stiffness matrix. The filter functions of the orthotropic material stiffness are deduced. Then these filter functions are put into buckling topology optimization of a differential equation to analyze the design sensitivity. Furthermore, the buckling constraints are approximately expressed as explicit functions with respect to the design variables based on the first-order Taylor expansion. The objective function is standardized based on the second-order Taylor expansion. Therefore, the optimization model is translated into a quadratic program. Finally, the dual sequence quadratic programming (DSQP) algorithm and the global convergence method of moving asymptotes algorithm with two different filter functions (CEF and PF) are applied to solve the optimal model. Three numerical results show that DSQP&CEF has the best performance in the view of structural mass and discretion.

Quantum-behaved particle swarm optimization for the synthesis of fibre Bragg gratings filter

NASA Astrophysics Data System (ADS)

Yu, Xuelian; Sun, Yunxu; Yao, Yong; Tian, Jiajun; Cong, Shan

2011-12-01

A method based on the quantum-behaved particle swarm optimization algorithm is presented to design a bandpass filter of the fibre Bragg gratings. In contrast to the other optimization algorithms such as the genetic algorithm and particle swarm optimization algorithm, this method is simpler and easier to implement. To demonstrate the effectiveness of the QPSO algorithm, we consider a bandpass filter. With the parameters the half the bandwidth of the filter 0.05 nm, the Bragg wavelength 1550 nm, the grating length with 2cm is divided into 40 uniform sections and its index modulation is what should be optimized and whole feasible solution space is searched for the index modulation. After the index modulation profile is known for all the sections, the transfer matrix method is used to verify the final optimal index modulation by calculating the refection spectrum. The results show the group delay is less than 12ps in band and the calculated dispersion is relatively flat inside the passband. It is further found that the reflective spectrum has sidelobes around -30dB and the worst in-band dispersion value is less than 200ps/nm . In addition, for this design, it takes approximately several minutes to find the acceptable index modulation values with a notebook computer.

On the Performance of the Martin Digital Filter for High- and Low-pass Applications

NASA Technical Reports Server (NTRS)

Mcclain, C. R.

1979-01-01

A nonrecursive numerical filter is described in which the weighting sequence is optimized by minimizing the excursion from the ideal rectangular filter in a least squares sense over the entire domain of normalized frequency. Additional corrections to the weights in order to reduce overshoot oscillations (Gibbs phenomenon) and to insure unity gain at zero frequency for the low pass filter are incorporated. The filter is characterized by a zero phase shift for all frequencies (due to a symmetric weighting sequence), a finite memory and stability, and it may readily be transformed to a high pass filter. Equations for the filter weights and the frequency response function are presented, and applications to high and low pass filtering are examined. A discussion of optimization of high pass filter parameters for a rather stringent response requirement is given in an application to the removal of aircraft low frequency oscillations superimposed on remotely sensed ocean surface profiles. Several frequency response functions are displayed, both in normalized frequency space and in period space. A comparison of the performance of the Martin filter with some other commonly used low pass digital filters is provided in an application to oceanographic data.

Optimization of plasma parameters with magnetic filter field and pressure to maximize H{sup −} ion density in a negative hydrogen ion source

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

Cho, Won-Hwi; Dang, Jeong-Jeung; Kim, June Young

2016-02-15

Transverse magnetic filter field as well as operating pressure is considered to be an important control knob to enhance negative hydrogen ion production via plasma parameter optimization in volume-produced negative hydrogen ion sources. Stronger filter field to reduce electron temperature sufficiently in the extraction region is favorable, but generally known to be limited by electron density drop near the extraction region. In this study, unexpected electron density increase instead of density drop is observed in front of the extraction region when the applied transverse filter field increases monotonically toward the extraction aperture. Measurements of plasma parameters with a movable Langmuirmore » probe indicate that the increased electron density may be caused by low energy electron accumulation in the filter region decreasing perpendicular diffusion coefficients across the increasing filter field. Negative hydrogen ion populations are estimated from the measured profiles of electron temperatures and densities and confirmed to be consistent with laser photo-detachment measurements of the H{sup −} populations for various filter field strengths and pressures. Enhanced H{sup −} population near the extraction region due to the increased low energy electrons in the filter region may be utilized to increase negative hydrogen beam currents by moving the extraction position accordingly. This new finding can be used to design efficient H{sup −} sources with an optimal filtering system by maximizing high energy electron filtering while keeping low energy electrons available in the extraction region.« less

Design Optimization of Vena Cava Filters: An application to dual filtration devices

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

Singer, M A; Wang, S L; Diachin, D P

Pulmonary embolism (PE) is a significant medical problem that results in over 300,000 fatalities per year. A common preventative treatment for PE is the insertion of a metallic filter into the inferior vena cava that traps thrombi before they reach the lungs. The goal of this work is to use methods of mathematical modeling and design optimization to determine the configuration of trapped thrombi that minimizes the hemodynamic disruption. The resulting configuration has implications for constructing an optimally designed vena cava filter. Computational fluid dynamics is coupled with a nonlinear optimization algorithm to determine the optimal configuration of trapped modelmore » thrombus in the inferior vena cava. The location and shape of the thrombus are parameterized, and an objective function, based on wall shear stresses, determines the worthiness of a given configuration. The methods are fully automated and demonstrate the capabilities of a design optimization framework that is broadly applicable. Changes to thrombus location and shape alter the velocity contours and wall shear stress profiles significantly. For vena cava filters that trap two thrombi simultaneously, the undesirable flow dynamics past one thrombus can be mitigated by leveraging the flow past the other thrombus. Streamlining the shape of thrombus trapped along the cava wall reduces the disruption to the flow, but increases the area exposed to abnormal wall shear stress. Computer-based design optimization is a useful tool for developing vena cava filters. Characterizing and parameterizing the design requirements and constraints is essential for constructing devices that address clinical complications. In addition, formulating a well-defined objective function that quantifies clinical risks and benefits is needed for designing devices that are clinically viable.« less

Study on a liquid-moderator-based neutron spectrometer for BNCT-Development and experimental test of the prototype spectrometer

NASA Astrophysics Data System (ADS)

Tamaki, S.; Sato, F.; Murata, I.

2017-10-01

Boron neutron capture therapy (BNCT) is known to be an effective radiation cancer therapy that requires neutron irradiation. A neutron field generated by an accelerator-based neutron source has various energy spectra, and it is necessary to evaluate the neutron spectrum in the treatment field. However, the method used to measure the neutron spectrum in the treatment field is not well established, and many researchers are making efforts to improve the spectrometers used. In the present study, we developed a prototype of a new neutron spectrometer that can measure the neutron spectra more accurately and precisely. The spectrometer is based on the same theory as that of the Bonner sphere spectrometer, and it uses a liquid moderator and an absorber. By carrying out an experimental test of the developed spectrometer, we finally revealed the problems and necessary conditions of the prototype detector.

a New Method to Measure 10B Uptake in Lung Adenocarcinoma in Hospital Bnct

NASA Astrophysics Data System (ADS)

Donegani, E. M.; Basilico, F.; Bolognini, D.; Borasio, P.; Capelli, E.; Cappelletti, P.; Chiari, P.; Frigerio, M.; Gelosa, S.; Giannini, G.; Hasan, S.; Mattera, A.; Mauri, P.; Monti, A. F.; Ostinelli, A.; Prest, M.; Vallazza, E.; Zanini, A.

2010-04-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapic technique still under development that could become crucial in the fight against some types of cancer (extended ones, located near vital organs or radio resistant). This binary technique requires the administration to the patient of a boron delivery agent and the irradiation with a thermal neutron beam. The high LET particles produced in the 10B(n,α)7Li reaction are exploited to destroy the tumour cells. This work presents a new system based on neutron autoradiography with a non-depleted self-triggering microstrip silicon detector, using a neutron beam produced by a hospital Linac. The system is fast, real time and allows the detection of 10B contents down to 25 ng. The main results on the study of 10B uptake in biological samples will be described in terms of kinetic curves (10B uptake as a function of time).

Design of almost symmetric orthogonal wavelet filter bank via direct optimization.

PubMed

Murugesan, Selvaraaju; Tay, David B H

2012-05-01

It is a well-known fact that (compact-support) dyadic wavelets [based on the two channel filter banks (FBs)] cannot be simultaneously orthogonal and symmetric. Although orthogonal wavelets have the energy preservation property, biorthogonal wavelets are preferred in image processing applications because of their symmetric property. In this paper, a novel method is presented for the design of almost symmetric orthogonal wavelet FB. Orthogonality is structurally imposed by using the unnormalized lattice structure, and this leads to an objective function, which is relatively simple to optimize. The designed filters have good frequency response, flat group delay, almost symmetric filter coefficients, and symmetric wavelet function.

Optimized Beam Sculpting with Generalized Fringe-rate Filters

NASA Astrophysics Data System (ADS)

Parsons, Aaron R.; Liu, Adrian; Ali, Zaki S.; Cheng, Carina

2016-03-01

We generalize the technique of fringe-rate filtering, whereby visibilities measured by a radio interferometer are re-weighted according to their temporal variation. As the Earth rotates, radio sources traverse through an interferometer’s fringe pattern at rates that depend on their position on the sky. Capitalizing on this geometric interpretation of fringe rates, we employ time-domain convolution kernels to enact fringe-rate filters that sculpt the effective primary beam of antennas in an interferometer. As we show, beam sculpting through fringe-rate filtering can be used to optimize measurements for a variety of applications, including mapmaking, minimizing polarization leakage, suppressing instrumental systematics, and enhancing the sensitivity of power-spectrum measurements. We show that fringe-rate filtering arises naturally in minimum variance treatments of many of these problems, enabling optimal visibility-based approaches to analyses of interferometric data that avoid systematics potentially introduced by traditional approaches such as imaging. Our techniques have recently been demonstrated in Ali et al., where new upper limits were placed on the 21 {cm} power spectrum from reionization, showcasing the ability of fringe-rate filtering to successfully boost sensitivity and reduce the impact of systematics in deep observations.

A Spectral Reconstruction Algorithm of Miniature Spectrometer Based on Sparse Optimization and Dictionary Learning.

PubMed

Zhang, Shang; Dong, Yuhan; Fu, Hongyan; Huang, Shao-Lun; Zhang, Lin

2018-02-22

The miniaturization of spectrometer can broaden the application area of spectrometry, which has huge academic and industrial value. Among various miniaturization approaches, filter-based miniaturization is a promising implementation by utilizing broadband filters with distinct transmission functions. Mathematically, filter-based spectral reconstruction can be modeled as solving a system of linear equations. In this paper, we propose an algorithm of spectral reconstruction based on sparse optimization and dictionary learning. To verify the feasibility of the reconstruction algorithm, we design and implement a simple prototype of a filter-based miniature spectrometer. The experimental results demonstrate that sparse optimization is well applicable to spectral reconstruction whether the spectra are directly sparse or not. As for the non-directly sparse spectra, their sparsity can be enhanced by dictionary learning. In conclusion, the proposed approach has a bright application prospect in fabricating a practical miniature spectrometer.

A Spectral Reconstruction Algorithm of Miniature Spectrometer Based on Sparse Optimization and Dictionary Learning

PubMed Central

Zhang, Shang; Fu, Hongyan; Huang, Shao-Lun; Zhang, Lin

2018-01-01

The miniaturization of spectrometer can broaden the application area of spectrometry, which has huge academic and industrial value. Among various miniaturization approaches, filter-based miniaturization is a promising implementation by utilizing broadband filters with distinct transmission functions. Mathematically, filter-based spectral reconstruction can be modeled as solving a system of linear equations. In this paper, we propose an algorithm of spectral reconstruction based on sparse optimization and dictionary learning. To verify the feasibility of the reconstruction algorithm, we design and implement a simple prototype of a filter-based miniature spectrometer. The experimental results demonstrate that sparse optimization is well applicable to spectral reconstruction whether the spectra are directly sparse or not. As for the non-directly sparse spectra, their sparsity can be enhanced by dictionary learning. In conclusion, the proposed approach has a bright application prospect in fabricating a practical miniature spectrometer. PMID:29470406

Classifying EEG for Brain-Computer Interface: Learning Optimal Filters for Dynamical System Features

PubMed Central

Song, Le; Epps, Julien

2007-01-01

Classification of multichannel EEG recordings during motor imagination has been exploited successfully for brain-computer interfaces (BCI). In this paper, we consider EEG signals as the outputs of a networked dynamical system (the cortex), and exploit synchronization features from the dynamical system for classification. Herein, we also propose a new framework for learning optimal filters automatically from the data, by employing a Fisher ratio criterion. Experimental evaluations comparing the proposed dynamical system features with the CSP and the AR features reveal their competitive performance during classification. Results also show the benefits of employing the spatial and the temporal filters optimized using the proposed learning approach. PMID:18364986

Introducing passive acoustic filter in acoustic based condition monitoring: Motor bike piston-bore fault identification

NASA Astrophysics Data System (ADS)

Jena, D. P.; Panigrahi, S. N.

2016-03-01

Requirement of designing a sophisticated digital band-pass filter in acoustic based condition monitoring has been eliminated by introducing a passive acoustic filter in the present work. So far, no one has attempted to explore the possibility of implementing passive acoustic filters in acoustic based condition monitoring as a pre-conditioner. In order to enhance the acoustic based condition monitoring, a passive acoustic band-pass filter has been designed and deployed. Towards achieving an efficient band-pass acoustic filter, a generalized design methodology has been proposed to design and optimize the desired acoustic filter using multiple filter components in series. An appropriate objective function has been identified for genetic algorithm (GA) based optimization technique with multiple design constraints. In addition, the sturdiness of the proposed method has been demonstrated in designing a band-pass filter by using an n-branch Quincke tube, a high pass filter and multiple Helmholtz resonators. The performance of the designed acoustic band-pass filter has been shown by investigating the piston-bore defect of a motor-bike using engine noise signature. On the introducing a passive acoustic filter in acoustic based condition monitoring reveals the enhancement in machine learning based fault identification practice significantly. This is also a first attempt of its own kind.

Control optimization, stabilization and computer algorithms for aircraft applications

NASA Technical Reports Server (NTRS)

1975-01-01

Research related to reliable aircraft design is summarized. Topics discussed include systems reliability optimization, failure detection algorithms, analysis of nonlinear filters, design of compensators incorporating time delays, digital compensator design, estimation for systems with echoes, low-order compensator design, descent-phase controller for 4-D navigation, infinite dimensional mathematical programming problems and optimal control problems with constraints, robust compensator design, numerical methods for the Lyapunov equations, and perturbation methods in linear filtering and control.

Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model.

PubMed

Iguchi, Yoshiya; Michiue, Hiroyuki; Kitamatsu, Mizuki; Hayashi, Yuri; Takenaka, Fumiaki; Nishiki, Tei-Ichi; Matsui, Hideki

2015-07-01

Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH](2-)2Na(+), BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake in vitro and in vivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells in vitro and in vivo. Furthermore, to monitor the pharmacokinetic properties of these agents in vivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with (64)Cu. We administered BSH-DOTA-(64)Cu and BSH-3R-DOTA-(64)Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical lessons from the first applications of BNCT on unresectable liver metastases.

NASA Astrophysics Data System (ADS)

Zonta, A.; Prati, U.; Roveda, L.; Ferrari, C.; Zonta, S.; Clerici, Am; Zonta, C.; Pinelli, T.; Fossati, F.; Altieri, S.; Bortolussi, S.; Bruschi, P.; Nano, R.; Barni, S.; Chiari, P.; Mazzini, G.

2006-05-01

After a long series of studies on the effects of neutron irradiation of 10B loaded neoplastic cells both in culture and in animal experiments, we started the clinical application of BNCT on humans affected by liver metastases of a radically resected colon adenocarcinoma. The procedure we adopted includes a first surgical phase, with hepatectomy; a radiotherapeutic phase, in which the isolated liver, washed and chilled, is extracorporeally irradiated with thermal neutrons; and then a second surgical phase for the reconnection of the liver to the patient. Until now two patients have been subjected to the BNCT treatment. The first one survived 44 months with a good quality of life, and died because of diffuse recurrences of his intestinal tumour. The second patient had the same early perioperative course, but after 33 days a worsening of a dilatative cardiomyopaty, from which he was suffering, determined a cardiac failure and eventually death. This clinical experience, although limited, has shown that extracorporeal neutron irradiation of the liver is a feasible procedure, able to ensure the complete destruction of liver metastases and a possible long lasting survival. In our patients neutron irradiation caused massive cellular necrosis highly specific to tumour cells, whereas normal cells were mostly spared. Nevertheless, the impact of such a traumatic operation on the patient's organism must be taken into account. Finally, we have to be aware that the fight against tumour rarely leads to a complete victory. We now have an innovative weapon which is both powerful and partly unsettled: it must be refined and above all used.

Development of liquid-lithium film jet-flow for the target of (7)Li(p,n)(7)Be reactions for BNCT.

PubMed

Kobayashi, Tooru; Miura, Kuniaki; Hayashizaki, Noriyosu; Aritomi, Masanori

2014-06-01

A feasibility study on liquid lithium target in the form of a flowing film was performed to evaluate its potential use as a neutron generation target of (7)Li(p,n)(7)Be reaction in BNCT. The target is a windowless-type flowing film on a concave wall. Its configuration was adapted for a proton beam which is 30mm in diameter and with energy and current of up to 3MeV and 20mA, respectively. The flowing film of liquid lithium was 0.6mm in thickness, 50mm in width and 50mm in length. The shapes of the nozzle and concave back wall, which create a stable flowing film jet, were decided based on water experiments. A lithium hydrodynamic experiment was performed to observe the stability of liquid lithium flow behavior. The flowing film of liquid lithium was found to be feasible at temperatures below the liquid lithium boiling saturation of 342°C at the surface pressure of 1×10(-3)Pa. Using a proto-type liquid lithium-circulating loop for BNCT, the stability of the film flow was confirmed for velocities up to 30m/s at 220°C and 250°C in vacuum at a pressure lower than 10(-3) Pa. It is expected that for practical use, a flowing liquid lithium target of a windowless type can solve the problem of radiation damage and target cooling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neutron generator for BNCT based on high current ECR ion source with gyrotron plasma heating.

PubMed

Skalyga, V; Izotov, I; Golubev, S; Razin, S; Sidorov, A; Maslennikova, A; Volovecky, A; Kalvas, T; Koivisto, H; Tarvainen, O

2015-12-01

BNCT development nowadays is constrained by a progress in neutron sources design. Creation of a cheap and compact intense neutron source would significantly simplify trial treatments avoiding use of expensive and complicated nuclear reactors and accelerators. D-D or D-T neutron generator is one of alternative types of such sources for. A so-called high current quasi-gasdynamic ECR ion source with plasma heating by millimeter wave gyrotron radiation is suggested to be used in a scheme of D-D neutron generator in the present work. Ion source of that type was developed in the Institute of Applied Physics of Russian Academy of Sciences (Nizhny Novgorod, Russia). It can produce deuteron ion beams with current density up to 700-800 mA/cm(2). Generation of the neutron flux with density at the level of 7-8·10(10) s(-1) cm(-2) at the target surface could be obtained in case of TiD2 target bombardment with deuteron beam accelerated to 100 keV. Estimations show that it is enough for formation of epithermal neutron flux with density higher than 10(9) s(-1) cm(-2) suitable for BNCT. Important advantage of described approach is absence of Tritium in the scheme. First experiments performed in pulsed regime with 300 mA, 45 kV deuteron beam directed to D2O target demonstrated 10(9) s(-1) neutron flux. This value corresponds to theoretical estimations and proofs prospects of neutron generator development based on high current quasi-gasdynamic ECR ion source. Copyright © 2015 Elsevier Ltd. All rights reserved.

Teaching learning based optimization-functional link artificial neural network filter for mixed noise reduction from magnetic resonance image.

PubMed

Kumar, M; Mishra, S K

2017-01-01

The clinical magnetic resonance imaging (MRI) images may get corrupted due to the presence of the mixture of different types of noises such as Rician, Gaussian, impulse, etc. Most of the available filtering algorithms are noise specific, linear, and non-adaptive. There is a need to develop a nonlinear adaptive filter that adapts itself according to the requirement and effectively applied for suppression of mixed noise from different MRI images. In view of this, a novel nonlinear neural network based adaptive filter i.e. functional link artificial neural network (FLANN) whose weights are trained by a recently developed derivative free meta-heuristic technique i.e. teaching learning based optimization (TLBO) is proposed and implemented. The performance of the proposed filter is compared with five other adaptive filters and analyzed by considering quantitative metrics and evaluating the nonparametric statistical test. The convergence curve and computational time are also included for investigating the efficiency of the proposed as well as competitive filters. The simulation outcomes of proposed filter outperform the other adaptive filters. The proposed filter can be hybridized with other evolutionary technique and utilized for removing different noise and artifacts from others medical images more competently.

Technical note: optimization for improved tube-loading efficiency in the dual-energy computed tomography coupled with balanced filter method.

PubMed

Saito, Masatoshi

2010-08-01

This article describes the spectral optimization of dual-energy computed tomography using balanced filters (bf-DECT) to reduce the tube loadings and dose by dedicating to the acquisition of electron density information, which is essential for treatment planning in radiotherapy. For the spectral optimization of bf-DECT, the author calculated the beam-hardening error and air kerma required to achieve a desired noise level in an electron density image of a 50-cm-diameter cylindrical water phantom. The calculation enables the selection of beam parameters such as tube voltage, balanced filter material, and its thickness. The optimal combination of tube voltages was 80 kV/140 kV in conjunction with Tb/Hf and Bi/Mo filter pairs; this combination agrees with that obtained in a previous study [M. Saito, "Spectral optimization for measuring electron density by the dual-energy computed tomography coupled with balanced filter method," Med. Phys. 36, 3631-3642 (2009)], although the thicknesses of the filters that yielded a minimum tube output were slightly different from those obtained in the previous study. The resultant tube loading of a low-energy scan of the present bf-DECT significantly decreased from 57.5 to 4.5 times that of a high-energy scan for conventional DECT. Furthermore, the air kerma of bf-DECT could be reduced to less than that of conventional DECT, while obtaining the same figure of merit for the measurement of electron density and effective atomic number. The tube-loading and dose efficiencies of bf-DECT were considerably improved by sacrificing the quality of the noise level in the images of effective atomic number.

Design and experimentally measure a high performance metamaterial filter

NASA Astrophysics Data System (ADS)

Xu, Ya-wen; Xu, Jing-cheng

2018-03-01

Metamaterial filter is a kind of expecting optoelectronic device. In this paper, a metal/dielectric/metal (M/D/M) structure metamaterial filter is simulated and measured. Simulated results indicate that the perfect impedance matching condition between the metamaterial filter and the free space leads to the transmission band. Measured results show that the proposed metamaterial filter achieves high performance transmission on TM and TE polarization directions. Moreover, the high transmission rate is also can be obtained when the incident angle reaches to 45°. Further measured results show that the transmission band can be expanded through optimizing structural parameters. The central frequency of the transmission band is also can be adjusted through optimizing structural parameters. The physical mechanism behind the central frequency shifted is solved through establishing an equivalent resonant circuit model.

Comparison of the image-derived radioactivity and blood-sample radioactivity for estimating the clinical indicators of the efficacy of boron neutron capture therapy (BNCT): 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET study.

PubMed

Isohashi, Kayako; Shimosegawa, Eku; Naka, Sadahiro; Kanai, Yasukazu; Horitsugi, Genki; Mochida, Ikuko; Matsunaga, Keiko; Watabe, Tadashi; Kato, Hiroki; Tatsumi, Mitsuaki; Hatazawa, Jun

2016-12-01

In boron neutron capture therapy (BNCT), positron emission tomography (PET) with 4-borono-2- 18 F-fluoro-phenylalanine (FBPA) is the only method to estimate an accumulation of 10 B to target tumor and surrounding normal tissue after administering 10 B carrier of L-paraboronophenylalanine and to search the indication of BNCT for individual patient. Absolute concentration of 10 B in tumor has been estimated by multiplying 10 B concentration in blood during BNCT by tumor to blood radioactivity (T/B) ratio derived from FBPA PET. However, the method to measure blood radioactivity either by blood sampling or image data has not been standardized. We compared image-derived blood radioactivity of FBPA with blood sampling data and studied appropriate timing and location for measuring image-derived blood counts. We obtained 7 repeated whole-body PET scans in five healthy subjects. Arterialized venous blood samples were obtained from the antecubital vein, heated in a heating blanket. Time-activity curves (TACs) of image-derived blood radioactivity were obtained using volumes of interest (VOIs) over ascending aorta, aortic arch, pulmonary artery, left and right ventricles, inferior vena cava, and abdominal aorta. Image-derived blood radioactivity was compared with those measured by blood sampling data in each location. Both the TACs of blood sampling radioactivity in each subject, and the TACs of image-derived blood radioactivity showed a peak within 5 min after the tracer injection, and promptly decreased soon thereafter. Linear relationship was found between blood sampling radioactivity and image-derived blood radioactivity in all the VOIs at any timing of data sampling (p < 0.001). Image-derived radioactivity measured in the left and right ventricles 30 min after injection showed high correlation with blood radioactivity. Image-derived blood radioactivity was lower than blood sampling radioactivity data by 20 %. Reduction of blood radioactivity of FBPA in left ventricle after 30 min of FBPA injection was minimal. We conclude that the image-derived T/B ratio can be reliably used by setting the VOI on the left ventricle at 30 min after FBPA administration and correcting for underestimation due to partial volume effect and reduction of FBPA blood radioactivity.

First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

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

Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.a; National Research Council; Crivello, Martin

2011-01-01

Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ({sup 10}BPA) and for 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX ({sup 10}BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm {sup 10}B) + neutrons, (2) BOPP (10 ppm {sup 10}B) + neutrons, (3) neutrons alone, and (4) gammamore » rays ({sup 60}Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy ({+-}10%) (thermal neutrons flux = 7.5 10{sup 9} n/cm{sup 2} sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 {+-} 1.1 and 2.4 {+-} 0.6; CBE for BOPP: 8.0 {+-} 2.2 and 2.0 {+-} 1; CBE for BPA: 19.6 {+-} 3.7 and 3.5 {+-} 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma.« less

Optimally Distributed Kalman Filtering with Data-Driven Communication †

PubMed Central

Dormann, Katharina

2018-01-01

For multisensor data fusion, distributed state estimation techniques that enable a local processing of sensor data are the means of choice in order to minimize storage and communication costs. In particular, a distributed implementation of the optimal Kalman filter has recently been developed. A significant disadvantage of this algorithm is that the fusion center needs access to each node so as to compute a consistent state estimate, which requires full communication each time an estimate is requested. In this article, different extensions of the optimally distributed Kalman filter are proposed that employ data-driven transmission schemes in order to reduce communication expenses. As a first relaxation of the full-rate communication scheme, it can be shown that each node only has to transmit every second time step without endangering consistency of the fusion result. Also, two data-driven algorithms are introduced that even allow for lower transmission rates, and bounds are derived to guarantee consistent fusion results. Simulations demonstrate that the data-driven distributed filtering schemes can outperform a centralized Kalman filter that requires each measurement to be sent to the center node. PMID:29596392

An optimized Kalman filter for the estimate of trunk orientation from inertial sensors data during treadmill walking.

PubMed

Mazzà, Claudia; Donati, Marco; McCamley, John; Picerno, Pietro; Cappozzo, Aurelio

2012-01-01

The aim of this study was the fine tuning of a Kalman filter with the intent to provide optimal estimates of lower trunk orientation in the frontal and sagittal planes during treadmill walking at different speeds using measured linear acceleration and angular velocity components represented in a local system of reference. Data were simultaneously collected using both an inertial measurement unit (IMU) and a stereophotogrammetric system from three healthy subjects walking on a treadmill at natural, slow and fast speeds. These data were used to estimate the parameters of the Kalman filter that minimized the difference between the trunk orientations provided by the filter and those obtained through stereophotogrammetry. The optimized parameters were then used to process the data collected from a further 15 healthy subjects of both genders and different anthropometry performing the same walking tasks with the aim of determining the robustness of the filter set up. The filter proved to be very robust. The root mean square values of the differences between the angles estimated through the IMU and through stereophotogrammetry were lower than 1.0° and the correlation coefficients between the corresponding curves were greater than 0.91. The proposed filter design can be used to reliably estimate trunk lateral and frontal bending during walking from inertial sensor data. Further studies are needed to determine the filter parameters that are most suitable for other motor tasks. Copyright © 2011. Published by Elsevier B.V.

Recursive Implementations of the Consider Filter

NASA Technical Reports Server (NTRS)

Zanetti, Renato; DSouza, Chris

2012-01-01

One method to account for parameters errors in the Kalman filter is to consider their effect in the so-called Schmidt-Kalman filter. This work addresses issues that arise when implementing a consider Kalman filter as a real-time, recursive algorithm. A favorite implementation of the Kalman filter as an onboard navigation subsystem is the UDU formulation. A new way to implement a UDU consider filter is proposed. The non-optimality of the recursive consider filter is also analyzed, and a modified algorithm is proposed to overcome this limitation.

Optimizing dual-energy x-ray parameters for the ExacTrac clinical stereoscopic imaging system to enhance soft-tissue imaging.

PubMed

Bowman, Wesley A; Robar, James L; Sattarivand, Mike

2017-03-01

Stereoscopic x-ray image guided radiotherapy for lung tumors is often hindered by bone overlap and limited soft-tissue contrast. This study aims to evaluate the feasibility of dual-energy imaging techniques and to optimize parameters of the ExacTrac stereoscopic imaging system to enhance soft-tissue imaging for application to lung stereotactic body radiation therapy. Simulated spectra and a physical lung phantom were used to optimize filter material, thickness, tube potentials, and weighting factors to obtain bone subtracted dual-energy images. Spektr simulations were used to identify material in the atomic number range (3-83) based on a metric defined to separate spectra of high and low-energies. Both energies used the same filter due to time constraints of imaging in the presence of respiratory motion. The lung phantom contained bone, soft tissue, and tumor mimicking materials, and it was imaged with a filter thickness in the range of (0-0.7) mm and a kVp range of (60-80) for low energy and (120,140) for high energy. Optimal dual-energy weighting factors were obtained when the bone to soft-tissue contrast-to-noise ratio (CNR) was minimized. Optimal filter thickness and tube potential were achieved by maximizing tumor-to-background CNR. Using the optimized parameters, dual-energy images of an anthropomorphic Rando phantom with a spherical tumor mimicking material inserted in his lung were acquired and evaluated for bone subtraction and tumor contrast. Imaging dose was measured using the dual-energy technique with and without beam filtration and matched to that of a clinical conventional single energy technique. Tin was the material of choice for beam filtering providing the best energy separation, non-toxicity, and non-reactiveness. The best soft-tissue-weighted image in the lung phantom was obtained using 0.2 mm tin and (140, 60) kVp pair. Dual-energy images of the Rando phantom with the tin filter had noticeable improvement in bone elimination, tumor contrast, and noise content when compared to dual-energy imaging with no filtration. The surface dose was 0.52 mGy per each stereoscopic view for both clinical single energy technique and the dual-energy technique in both cases of with and without the tin filter. Dual-energy soft-tissue imaging is feasible without additional imaging dose using the ExacTrac stereoscopic imaging system with optimized acquisition parameters and no beam filtration. Addition of a single tin filter for both the high and low energies has noticeable improvements on dual-energy imaging with optimized parameters. Clinical implementation of a dual-energy technique on ExacTrac stereoscopic imaging could improve lung tumor visibility. © 2017 American Association of Physicists in Medicine.

Recent Results on "Approximations to Optimal Alarm Systems for Anomaly Detection"

NASA Technical Reports Server (NTRS)

Martin, Rodney Alexander

2009-01-01

An optimal alarm system and its approximations may use Kalman filtering for univariate linear dynamic systems driven by Gaussian noise to provide a layer of predictive capability. Predicted Kalman filter future process values and a fixed critical threshold can be used to construct a candidate level-crossing event over a predetermined prediction window. An optimal alarm system can be designed to elicit the fewest false alarms for a fixed detection probability in this particular scenario.

Dual Adaptive Filtering by Optimal Projection Applied to Filter Muscle Artifacts on EEG and Comparative Study

PubMed Central

Peyrodie, Laurent; Szurhaj, William; Bolo, Nicolas; Pinti, Antonio; Gallois, Philippe

2014-01-01

Muscle artifacts constitute one of the major problems in electroencephalogram (EEG) examinations, particularly for the diagnosis of epilepsy, where pathological rhythms occur within the same frequency bands as those of artifacts. This paper proposes to use the method dual adaptive filtering by optimal projection (DAFOP) to automatically remove artifacts while preserving true cerebral signals. DAFOP is a two-step method. The first step consists in applying the common spatial pattern (CSP) method to two frequency windows to identify the slowest components which will be considered as cerebral sources. The two frequency windows are defined by optimizing convolutional filters. The second step consists in using a regression method to reconstruct the signal independently within various frequency windows. This method was evaluated by two neurologists on a selection of 114 pages with muscle artifacts, from 20 clinical recordings of awake and sleeping adults, subject to pathological signals and epileptic seizures. A blind comparison was then conducted with the canonical correlation analysis (CCA) method and conventional low-pass filtering at 30 Hz. The filtering rate was 84.3% for muscle artifacts with a 6.4% reduction of cerebral signals even for the fastest waves. DAFOP was found to be significantly more efficient than CCA and 30 Hz filters. The DAFOP method is fast and automatic and can be easily used in clinical EEG recordings. PMID:25298967

Design optimization of integrated BiDi triplexer optical filter based on planar lightwave circuit.

PubMed

Xu, Chenglin; Hong, Xiaobin; Huang, Wei-Ping

2006-05-29

Design optimization of a novel integrated bi-directional (BiDi) triplexer filter based on planar lightwave circuit (PLC) for fiber-to-the premise (FTTP) applications is described. A multi-mode interference (MMI) device is used to filter the up-stream 1310nm signal from the down-stream 1490nm and 1555nm signals. An array waveguide grating (AWG) device performs the dense WDM function by further separating the two down-stream signals. The MMI and AWG are built on the same substrate with monolithic integration. The design is validated by simulation, which shows excellent performance in terms of filter spectral characteristics (e.g., bandwidth, cross-talk, etc.) as well as insertion loss.

Design optimization of integrated BiDi triplexer optical filter based on planar lightwave circuit

NASA Astrophysics Data System (ADS)

Xu, Chenglin; Hong, Xiaobin; Huang, Wei-Ping

2006-05-01

Design optimization of a novel integrated bi-directional (BiDi) triplexer filter based on planar lightwave circuit (PLC) for fiber-to-the premise (FTTP) applications is described. A multi-mode interference (MMI) device is used to filter the up-stream 1310nm signal from the down-stream 1490nm and 1555nm signals. An array waveguide grating (AWG) device performs the dense WDM function by further separating the two down-stream signals. The MMI and AWG are built on the same substrate with monolithic integration. The design is validated by simulation, which shows excellent performance in terms of filter spectral characteristics (e.g., bandwidth, cross-talk, etc.) as well as insertion loss.

Analytically solvable chaotic oscillator based on a first-order filter.

PubMed

Corron, Ned J; Cooper, Roy M; Blakely, Jonathan N

2016-02-01

A chaotic hybrid dynamical system is introduced and its analytic solution is derived. The system is described as an unstable first order filter subject to occasional switching of a set point according to a feedback rule. The system qualitatively differs from other recently studied solvable chaotic hybrid systems in that the timing of the switching is regulated by an external clock. The chaotic analytic solution is an optimal waveform for communications in noise when a resistor-capacitor-integrate-and-dump filter is used as a receiver. As such, these results provide evidence in support of a recent conjecture that the optimal communication waveform for any stable infinite-impulse response filter is chaotic.

Analytically solvable chaotic oscillator based on a first-order filter

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

Corron, Ned J.; Cooper, Roy M.; Blakely, Jonathan N.

2016-02-15

A chaotic hybrid dynamical system is introduced and its analytic solution is derived. The system is described as an unstable first order filter subject to occasional switching of a set point according to a feedback rule. The system qualitatively differs from other recently studied solvable chaotic hybrid systems in that the timing of the switching is regulated by an external clock. The chaotic analytic solution is an optimal waveform for communications in noise when a resistor-capacitor-integrate-and-dump filter is used as a receiver. As such, these results provide evidence in support of a recent conjecture that the optimal communication waveform formore » any stable infinite-impulse response filter is chaotic.« less

An exact algorithm for optimal MAE stack filter design.

PubMed

Dellamonica, Domingos; Silva, Paulo J S; Humes, Carlos; Hirata, Nina S T; Barrera, Junior

2007-02-01

We propose a new algorithm for optimal MAE stack filter design. It is based on three main ingredients. First, we show that the dual of the integer programming formulation of the filter design problem is a minimum cost network flow problem. Next, we present a decomposition principle that can be used to break this dual problem into smaller subproblems. Finally, we propose a specialization of the network Simplex algorithm based on column generation to solve these smaller subproblems. Using our method, we were able to efficiently solve instances of the filter problem with window size up to 25 pixels. To the best of our knowledge, this is the largest dimension for which this problem was ever solved exactly.

Design of efficient circularly symmetric two-dimensional variable digital FIR filters.

PubMed

Bindima, Thayyil; Elias, Elizabeth

2016-05-01

Circularly symmetric two-dimensional (2D) finite impulse response (FIR) filters find extensive use in image and medical applications, especially for isotropic filtering. Moreover, the design and implementation of 2D digital filters with variable fractional delay and variable magnitude responses without redesigning the filter has become a crucial topic of interest due to its significance in low-cost applications. Recently the design using fixed word length coefficients has gained importance due to the replacement of multipliers by shifters and adders, which reduces the hardware complexity. Among the various approaches to 2D design, transforming a one-dimensional (1D) filter to 2D by transformation, is reported to be an efficient technique. In this paper, 1D variable digital filters (VDFs) with tunable cut-off frequencies are designed using Farrow structure based interpolation approach, and the sub-filter coefficients in the Farrow structure are made multiplier-less using canonic signed digit (CSD) representation. The resulting performance degradation in the filters is overcome by using artificial bee colony (ABC) optimization. Finally, the optimized 1D VDFs are mapped to 2D using generalized McClellan transformation resulting in low complexity, circularly symmetric 2D VDFs with real-time tunability.

Design of efficient circularly symmetric two-dimensional variable digital FIR filters

PubMed Central

Bindima, Thayyil; Elias, Elizabeth

2016-01-01

Circularly symmetric two-dimensional (2D) finite impulse response (FIR) filters find extensive use in image and medical applications, especially for isotropic filtering. Moreover, the design and implementation of 2D digital filters with variable fractional delay and variable magnitude responses without redesigning the filter has become a crucial topic of interest due to its significance in low-cost applications. Recently the design using fixed word length coefficients has gained importance due to the replacement of multipliers by shifters and adders, which reduces the hardware complexity. Among the various approaches to 2D design, transforming a one-dimensional (1D) filter to 2D by transformation, is reported to be an efficient technique. In this paper, 1D variable digital filters (VDFs) with tunable cut-off frequencies are designed using Farrow structure based interpolation approach, and the sub-filter coefficients in the Farrow structure are made multiplier-less using canonic signed digit (CSD) representation. The resulting performance degradation in the filters is overcome by using artificial bee colony (ABC) optimization. Finally, the optimized 1D VDFs are mapped to 2D using generalized McClellan transformation resulting in low complexity, circularly symmetric 2D VDFs with real-time tunability. PMID:27222739

The Use of Daily Geodetic UT1 and LOD Data in the Optimal Estimation of UT1 and LOD With the JPL Kalman Earth Orientation Filter

NASA Technical Reports Server (NTRS)

Freedman, A. P.; Steppe, J. A.

1995-01-01

The Jet Propulsion Laboratory Kalman Earth Orientation Filter (KEOF) uses several of the Earth rotation data sets available to generate optimally interpolated UT1 and LOD series to support spacecraft navigation. This paper compares use of various data sets within KEOF.

Optimality based repetitive controller design for track-following servo system of optical disk drives.

PubMed

Chen, Wentao; Zhang, Weidong

2009-10-01

In an optical disk drive servo system, to attenuate the external periodic disturbances induced by inevitable disk eccentricity, repetitive control has been used successfully. The performance of a repetitive controller greatly depends on the bandwidth of the low-pass filter included in the repetitive controller. However, owing to the plant uncertainty and system stability, it is difficult to maximize the bandwidth of the low-pass filter. In this paper, we propose an optimality based repetitive controller design method for the track-following servo system with norm-bounded uncertainties. By embedding a lead compensator in the repetitive controller, both the system gain at periodic signal's harmonics and the bandwidth of the low-pass filter are greatly increased. The optimal values of the repetitive controller's parameters are obtained by solving two optimization problems. Simulation and experimental results are provided to illustrate the effectiveness of the proposed method.

Comparison of Kalman filter and optimal smoother estimates of spacecraft attitude

NASA Technical Reports Server (NTRS)

Sedlak, J.

1994-01-01

Given a valid system model and adequate observability, a Kalman filter will converge toward the true system state with error statistics given by the estimated error covariance matrix. The errors generally do not continue to decrease. Rather, a balance is reached between the gain of information from new measurements and the loss of information during propagation. The errors can be further reduced, however, by a second pass through the data with an optimal smoother. This algorithm obtains the optimally weighted average of forward and backward propagating Kalman filters. It roughly halves the error covariance by including future as well as past measurements in each estimate. This paper investigates whether such benefits actually accrue in the application of an optimal smoother to spacecraft attitude determination. Tests are performed both with actual spacecraft data from the Extreme Ultraviolet Explorer (EUVE) and with simulated data for which the true state vector and noise statistics are exactly known.

Selection of optimal spectral sensitivity functions for color filter arrays.

PubMed

Parmar, Manu; Reeves, Stanley J

2010-12-01

A color image meant for human consumption can be appropriately displayed only if at least three distinct color channels are present. Typical digital cameras acquire three-color images with only one sensor. A color filter array (CFA) is placed on the sensor such that only one color is sampled at a particular spatial location. This sparsely sampled signal is then reconstructed to form a color image with information about all three colors at each location. In this paper, we show that the wavelength sensitivity functions of the CFA color filters affect both the color reproduction ability and the spatial reconstruction quality of recovered images. We present a method to select perceptually optimal color filter sensitivity functions based upon a unified spatial-chromatic sampling framework. A cost function independent of particular scenes is defined that expresses the error between a scene viewed by the human visual system and the reconstructed image that represents the scene. A constrained minimization of the cost function is used to obtain optimal values of color-filter sensitivity functions for several periodic CFAs. The sensitivity functions are shown to perform better than typical RGB and CMY color filters in terms of both the s-CIELAB ∆E error metric and a qualitative assessment.

Optimal Matched Filter in the Low-number Count Poisson Noise Regime and Implications for X-Ray Source Detection

NASA Astrophysics Data System (ADS)

Ofek, Eran O.; Zackay, Barak

2018-04-01

Detection of templates (e.g., sources) embedded in low-number count Poisson noise is a common problem in astrophysics. Examples include source detection in X-ray images, γ-rays, UV, neutrinos, and search for clusters of galaxies and stellar streams. However, the solutions in the X-ray-related literature are sub-optimal in some cases by considerable factors. Using the lemma of Neyman–Pearson, we derive the optimal statistics for template detection in the presence of Poisson noise. We demonstrate that, for known template shape (e.g., point sources), this method provides higher completeness, for a fixed false-alarm probability value, compared with filtering the image with the point-spread function (PSF). In turn, we find that filtering by the PSF is better than filtering the image using the Mexican-hat wavelet (used by wavdetect). For some background levels, our method improves the sensitivity of source detection by more than a factor of two over the popular Mexican-hat wavelet filtering. This filtering technique can also be used for fast PSF photometry and flare detection; it is efficient and straightforward to implement. We provide an implementation in MATLAB. The development of a complete code that works on real data, including the complexities of background subtraction and PSF variations, is deferred for future publication.

Precision of proportion estimation with binary compressed Raman spectrum.

PubMed

Réfrégier, Philippe; Scotté, Camille; de Aguiar, Hilton B; Rigneault, Hervé; Galland, Frédéric

2018-01-01

The precision of proportion estimation with binary filtering of a Raman spectrum mixture is analyzed when the number of binary filters is equal to the number of present species and when the measurements are corrupted with Poisson photon noise. It is shown that the Cramer-Rao bound provides a useful methodology to analyze the performance of such an approach, in particular when the binary filters are orthogonal. It is demonstrated that a simple linear mean square error estimation method is efficient (i.e., has a variance equal to the Cramer-Rao bound). Evolutions of the Cramer-Rao bound are analyzed when the measuring times are optimized or when the considered proportion for binary filter synthesis is not optimized. Two strategies for the appropriate choice of this considered proportion are also analyzed for the binary filter synthesis.

Nonlinear optimal filter technique for analyzing energy depositions in TES sensors driven into saturation

DOE PAGES

Shank, B.; Yen, J. J.; Cabrera, B.; ...

2014-11-04

We present a detailed thermal and electrical model of superconducting transition edge sensors (TESs) connected to quasiparticle (qp) traps, such as the W TESs connected to Al qp traps used for CDMS (Cryogenic Dark Matter Search) Ge and Si detectors. We show that this improved model, together with a straightforward time-domain optimal filter, can be used to analyze pulses well into the nonlinear saturation region and reconstruct absorbed energies with optimal energy resolution.

MEDOF - MINIMUM EUCLIDEAN DISTANCE OPTIMAL FILTER

NASA Technical Reports Server (NTRS)

Barton, R. S.

1994-01-01

The Minimum Euclidean Distance Optimal Filter program, MEDOF, generates filters for use in optical correlators. The algorithm implemented in MEDOF follows theory put forth by Richard D. Juday of NASA/JSC. This program analytically optimizes filters on arbitrary spatial light modulators such as coupled, binary, full complex, and fractional 2pi phase. MEDOF optimizes these modulators on a number of metrics including: correlation peak intensity at the origin for the centered appearance of the reference image in the input plane, signal to noise ratio including the correlation detector noise as well as the colored additive input noise, peak to correlation energy defined as the fraction of the signal energy passed by the filter that shows up in the correlation spot, and the peak to total energy which is a generalization of PCE that adds the passed colored input noise to the input image's passed energy. The user of MEDOF supplies the functions that describe the following quantities: 1) the reference signal, 2) the realizable complex encodings of both the input and filter SLM, 3) the noise model, possibly colored, as it adds at the reference image and at the correlation detection plane, and 4) the metric to analyze, here taken to be one of the analytical ones like SNR (signal to noise ratio) or PCE (peak to correlation energy) rather than peak to secondary ratio. MEDOF calculates filters for arbitrary modulators and a wide range of metrics as described above. MEDOF examines the statistics of the encoded input image's noise (if SNR or PCE is selected) and the filter SLM's (Spatial Light Modulator) available values. These statistics are used as the basis of a range for searching for the magnitude and phase of k, a pragmatically based complex constant for computing the filter transmittance from the electric field. The filter is produced for the mesh points in those ranges and the value of the metric that results from these points is computed. When the search is concluded, the values of amplitude and phase for the k whose metric was largest, as well as consistency checks, are reported. A finer search can be done in the neighborhood of the optimal k if desired. The filter finally selected is written to disk in terms of drive values, not in terms of the filter's complex transmittance. Optionally, the impulse response of the filter may be created to permit users to examine the response for the features the algorithm deems important to the recognition process under the selected metric, limitations of the filter SLM, etc. MEDOF uses the filter SLM to its greatest potential, therefore filter competence is not compromised for simplicity of computation. MEDOF is written in C-language for Sun series computers running SunOS. With slight modifications, it has been implemented on DEC VAX series computers using the DEC-C v3.30 compiler, although the documentation does not currently support this platform. MEDOF can also be compiled using Borland International Inc.'s Turbo C++ v1.0, but IBM PC memory restrictions greatly reduce the maximum size of the reference images from which the filters can be calculated. MEDOF requires a two dimensional Fast Fourier Transform (2DFFT). One 2DFFT routine which has been used successfully with MEDOF is a routine found in "Numerical Recipes in C: The Art of Scientific Programming," which is available from Cambridge University Press, New Rochelle, NY 10801. The standard distribution medium for MEDOF is a .25 inch streaming magnetic tape cartridge (Sun QIC-24) in UNIX tar format. MEDOF was developed in 1992-1993.

Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

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

Hawthorne, M. Frederick

2005-04-07

Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer,more » incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are amphiphilic unimolecular nanoparticles presenting several advantages: tunable size through functionalization and branching, spherical shape due to the icosahedral B122 core, promising water solubility resulting from degradation of all pendant closo-carborane groups to their hydrophilic nido anion substituents, and efficient boron delivery owing to the presence of 120 boron atoms which gives rise to a boron content as high as 40% by weight. Keeping the new objective in mind, we have focused on the design, synthesis and evaluation of new and very boron-rich closomer species. Additionally, progress has also been made toward the evaluation of a newly synthesized boron-rich lipid as a substitute for DSPC in bilayer construction, and the boron content of the resulting liposomes has been greatly enhanced. Related research involving the synthesis and self-assembly of carborane-containing amphiphiles has been systematically studied. Combined hydrophobic and hydrophilic properties of the single-chain amphiphiles allow their spontaneous self-assembly to form rods under a variety of variable conditions, such as concentration in the bilayer, carborane cage structure, chain-length, counterion identity, solvents, methods of preparation, and the ionic charge. On the other hand, the number of attached chains affects the self-assembly process. Particles having totally different shapes have been observed for dual-chain amphiphiles.« less

Design and fabrication of cascaded dichromate gelatin holographic filters for spectrum-splitting PV systems

NASA Astrophysics Data System (ADS)

Wu, Yuechen; Chrysler, Benjamin; Kostuk, Raymond K.

2018-01-01

The technique of designing, optimizing, and fabricating broadband volume transmission holograms using dichromate gelatin (DCG) is summarized for solar spectrum-splitting applications. The spectrum-splitting photovoltaic (PV) system uses a series of single-bandgap PV cells that have different spectral conversion efficiency properties to more fully utilize the solar spectrum. In such a system, one or more high-performance optical filters are usually required to split the solar spectrum and efficiently send them to the corresponding PV cells. An ideal spectral filter should have a rectangular shape with sharp transition wavelengths. A methodology of designing and modeling a transmission DCG hologram using coupled wave analysis for different PV bandgap combinations is described. To achieve a broad diffraction bandwidth and sharp cutoff wavelength, a cascaded structure of multiple thick holograms is described. A search algorithm is then developed to optimize both single- and two-layer cascaded holographic spectrum-splitting elements for the best bandgap combinations of two- and three-junction spectrum-splitting photovoltaic (SSPV) systems illuminated under the AM1.5 solar spectrum. The power conversion efficiencies of the optimized systems are found to be 42.56% and 48.41%, respectively, using the detailed balance method, and show an improvement compared with a tandem multijunction system. A fabrication method for cascaded DCG holographic filters is also described and used to prototype the optimized filter for the three-junction SSPV system.

Application of an Optimal Tuner Selection Approach for On-Board Self-Tuning Engine Models

NASA Technical Reports Server (NTRS)

Simon, Donald L.; Armstrong, Jeffrey B.; Garg, Sanjay

2012-01-01

An enhanced design methodology for minimizing the error in on-line Kalman filter-based aircraft engine performance estimation applications is presented in this paper. It specific-ally addresses the under-determined estimation problem, in which there are more unknown parameters than available sensor measurements. This work builds upon an existing technique for systematically selecting a model tuning parameter vector of appropriate dimension to enable estimation by a Kalman filter, while minimizing the estimation error in the parameters of interest. While the existing technique was optimized for open-loop engine operation at a fixed design point, in this paper an alternative formulation is presented that enables the technique to be optimized for an engine operating under closed-loop control throughout the flight envelope. The theoretical Kalman filter mean squared estimation error at a steady-state closed-loop operating point is derived, and the tuner selection approach applied to minimize this error is discussed. A technique for constructing a globally optimal tuning parameter vector, which enables full-envelope application of the technology, is also presented, along with design steps for adjusting the dynamic response of the Kalman filter state estimates. Results from the application of the technique to linear and nonlinear aircraft engine simulations are presented and compared to the conventional approach of tuner selection. The new methodology is shown to yield a significant improvement in on-line Kalman filter estimation accuracy.

Generalized filtering of laser fields in optimal control theory: application to symmetry filtering of quantum gate operations

NASA Astrophysics Data System (ADS)

Schröder, Markus; Brown, Alex

2009-10-01

We present a modified version of a previously published algorithm (Gollub et al 2008 Phys. Rev. Lett.101 073002) for obtaining an optimized laser field with more general restrictions on the search space of the optimal field. The modification leads to enforcement of the constraints on the optimal field while maintaining good convergence behaviour in most cases. We demonstrate the general applicability of the algorithm by imposing constraints on the temporal symmetry of the optimal fields. The temporal symmetry is used to reduce the number of transitions that have to be optimized for quantum gate operations that involve inversion (NOT gate) or partial inversion (Hadamard gate) of the qubits in a three-dimensional model of ammonia.

Design of a composite filter realizable on practical spatial light modulators

NASA Technical Reports Server (NTRS)

Rajan, P. K.; Ramakrishnan, Ramachandran

1994-01-01

Hybrid optical correlator systems use two spatial light modulators (SLM's), one at the input plane and the other at the filter plane. Currently available SLM's such as the deformable mirror device (DMD) and liquid crystal television (LCTV) SLM's exhibit arbitrarily constrained operating characteristics. The pattern recognition filters designed with the assumption that the SLM's have ideal operating characteristic may not behave as expected when implemented on the DMD or LCTV SLM's. Therefore it is necessary to incorporate the SLM constraints in the design of the filters. In this report, an iterative method is developed for the design of an unconstrained minimum average correlation energy (MACE) filter. Then using this algorithm a new approach for the design of a SLM constrained distortion invariant filter in the presence of input SLM is developed. Two different optimization algorithms are used to maximize the objective function during filter synthesis, one based on the simplex method and the other based on the Hooke and Jeeves method. Also, the simulated annealing based filter design algorithm proposed by Khan and Rajan is refined and improved. The performance of the filter is evaluated in terms of its recognition/discrimination capabilities using computer simulations and the results are compared with a simulated annealing optimization based MACE filter. The filters are designed for different LCTV SLM's operating characteristics and the correlation responses are compared. The distortion tolerance and the false class image discrimination qualities of the filter are comparable to those of the simulated annealing based filter but the new filter design takes about 1/6 of the computer time taken by the simulated annealing filter design.

Demonstration of differential phase-shift keying demodulation at 10 Gbit/s optimal fiber Bragg grating filters.

PubMed

Gatti, Davide; Galzerano, Gianluca; Laporta, Paolo; Longhi, Stefano; Janner, Davide; Guglierame, Andrea; Belmonte, Michele

2008-07-01

Optimal demodulation of differential phase-shift keying signals at 10 Gbit/s is experimentally demonstrated using a specially designed structured fiber Bragg grating composed by Fabry-Perot coupled cavities. Bit-error-rate measurements show that, as compared with a conventional Gaussian-shaped filter, our demodulator gives approximately 2.8 dB performance improvement.

Optimal causal inference: estimating stored information and approximating causal architecture.

PubMed

Still, Susanne; Crutchfield, James P; Ellison, Christopher J

2010-09-01

We introduce an approach to inferring the causal architecture of stochastic dynamical systems that extends rate-distortion theory to use causal shielding--a natural principle of learning. We study two distinct cases of causal inference: optimal causal filtering and optimal causal estimation. Filtering corresponds to the ideal case in which the probability distribution of measurement sequences is known, giving a principled method to approximate a system's causal structure at a desired level of representation. We show that in the limit in which a model-complexity constraint is relaxed, filtering finds the exact causal architecture of a stochastic dynamical system, known as the causal-state partition. From this, one can estimate the amount of historical information the process stores. More generally, causal filtering finds a graded model-complexity hierarchy of approximations to the causal architecture. Abrupt changes in the hierarchy, as a function of approximation, capture distinct scales of structural organization. For nonideal cases with finite data, we show how the correct number of the underlying causal states can be found by optimal causal estimation. A previously derived model-complexity control term allows us to correct for the effect of statistical fluctuations in probability estimates and thereby avoid overfitting.

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.

PubMed

Heber, Elisa M; Hawthorne, M Frederick; Kueffer, Peter J; Garabalino, Marcela A; Thorp, Silvia I; Pozzi, Emiliano C C; Monti Hughes, Andrea; Maitz, Charles A; Jalisatgi, Satish S; Nigg, David W; Curotto, Paula; Trivillin, Verónica A; Schwint, Amanda E

2014-11-11

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.

Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy

PubMed Central

Dewi, Novriana; Higashi, Syushi; Ikushima, Ichiro; Seguchi, Koji; Mizumachi, Ryoji; Murata, Yuji; Morishita, Yasuyuki; Shinohara, Atsuko; Mikado, Shoji; Yasuda, Nakahiro; Fujihara, Mitsuteru; Sakurai, Yuriko; Mouri, Kikue; Yanagawa, Masashi; Iizuka, Tomoya; Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shin-ichiro; Tanaka, Hiroki; Matsukawa, Takehisa; Yokoyama, Kazuhito; Fujino, Takashi; Ogura, Koichi; Nonaka, Yasumasa; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Yui, Sho; Nishimura, Ryohei; Ono, Koji; Takamoto, Sinichi; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Hasumi, Kenichiro; Takahashi, Hiroyuki

2017-01-01

Objective: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. Methods: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm−2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Results: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. Conclusion: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure. PMID:28406315

Radiation absorbed dose estimates for 18F-BPA PET.

PubMed

Kono, Yuzuru; Kurihara, Hiroaki; Kawamoto, Hiroshi; Yasui, Naoko; Honda, Naoki; Igaki, Hiroshi; Itami, Jun

2017-09-01

Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the 10 B (n, α) 7 Li nuclear reaction in cancer cells. In BNCT, delivery of 10 B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

PubMed Central

Heber, Elisa M.; Hawthorne, M. Frederick; Kueffer, Peter J.; Garabalino, Marcela A.; Thorp, Silvia I.; Pozzi, Emiliano C. C.; Hughes, Andrea Monti; Maitz, Charles A.; Jalisatgi, Satish S.; Nigg, David W.; Curotto, Paula; Trivillin, Verónica A.; Schwint, Amanda E.

2014-01-01

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70–88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70–88%. PMID:25349432

Avidin self-associates with boric acid gel suspensions: an affinity boron carrier that might be developed for boron neutron-capture therapy.

PubMed

Bench, Bennie J; Johnson, Rebecca; Hamilton, Craig; Gooch, Joey; Wright, John R

2004-02-15

It has been shown in preliminary studies that the antibacterial protein avidin self-associates with the boric acid gel polymer, and avidin-coated gel particles in the micrometer and submicrometer size ranges are of interest for boron neutron-capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce intense alpha radiation for tumor destruction. The gel particles carry large amounts of boron-10 and are theoretically able effect a meaningful tissue dosing through BNCT. A gross precipitation of gel particles occurs within 46 min of mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a minimum time if gel and avidin concentrations are in the low microgram/milliliter range, but at higher proportions of avidin the time delay to precipitation increases significantly; i.e., the colloid surface becomes blocked, inhibiting lattice formation. The avidin-coated gel particles eventually cross-link, forming a solid matrix and precipitating on a timescale measured on the order of an hour. At shorter exposure times rapid agglutination-like reactions were observed with biotinylated bovine albumin, suggesting that two-stage pretargeting of specific tissues should be possible with biotinylated antitumor antibodies. However, for BNCT to be practical, avidin's interaction with the gel needs to be strengthened, and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else the particles will interact strongly and nonspecifically with each other and with the carbohydrate groups present on most cell surfaces. Glyceric acid delays the precipitation of the particle suspensions while most simple and complex carbohydrates accelerate it.

Measurement of the 33S(n,α) cross-section at n_TOF(CERN): Applications to BNCT

PubMed Central

Sabaté-Gilarte, Marta; Praena, Javier; Porras, Ignacio; Quesada, José Manuel; Mastinu, Pierfrancesco

2016-01-01

Aim The main purpose of this work is to present a new (n,α) cross-section measurement for a stable isotope of sulfur, 33S, in order to solve existing discrepancies. Background 33S has been studied as a cooperating target for Boron Neutron Capture Therapy (BNCT) because of its large (n,α) cross-section in the epithermal neutron energy range, the most suitable one for BNCT. Although the most important evaluated databases, such as ENDF, do not show any resonances in the cross-section, experimental measurements which provided data from 10 keV to 1 MeV showed that the lowest-lying and strongest resonance of 33S(n,α) cross-section occurs at 13.5 keV. Nevertheless, the set of resonance parameters that describe such resonance shows important discrepancies (more than a factor of 2) between them. Materials and methods A new measurement of the 33S(n,α)30Si reaction cross-section was proposed to the ISOLDE and Neutron Time-of-Flight Experiments Committee of CERN. It was performed at n_TOF(CERN) in 2012 using MicroMegas detectors. Results In this work, we will present a brief overview of the experiment as well as preliminary results of the data analysis in the neutron energy range from thermal to 100 keV. These results will be taken into account to calculate the kerma-fluence factors corresponding to 33S in addition to 10B and those of a standard four-component ICRU tissue. Conclusions MCNP simulations of the deposited dose, including our experimental data, shows an important kerma rate enhancement at the surface of the tissue, mainly due to the presence of 33S. PMID:26933393

Measurement of the (33)S(n,α) cross-section at n_TOF(CERN): Applications to BNCT.

PubMed

Sabaté-Gilarte, Marta; Praena, Javier; Porras, Ignacio; Quesada, José Manuel; Mastinu, Pierfrancesco

2016-01-01

The main purpose of this work is to present a new (n,α) cross-section measurement for a stable isotope of sulfur, (33)S, in order to solve existing discrepancies. (33)S has been studied as a cooperating target for Boron Neutron Capture Therapy (BNCT) because of its large (n,α) cross-section in the epithermal neutron energy range, the most suitable one for BNCT. Although the most important evaluated databases, such as ENDF, do not show any resonances in the cross-section, experimental measurements which provided data from 10 keV to 1 MeV showed that the lowest-lying and strongest resonance of (33)S(n,α) cross-section occurs at 13.5 keV. Nevertheless, the set of resonance parameters that describe such resonance shows important discrepancies (more than a factor of 2) between them. A new measurement of the (33)S(n,α)(30)Si reaction cross-section was proposed to the ISOLDE and Neutron Time-of-Flight Experiments Committee of CERN. It was performed at n_TOF(CERN) in 2012 using MicroMegas detectors. In this work, we will present a brief overview of the experiment as well as preliminary results of the data analysis in the neutron energy range from thermal to 100 keV. These results will be taken into account to calculate the kerma-fluence factors corresponding to (33)S in addition to (10)B and those of a standard four-component ICRU tissue. MCNP simulations of the deposited dose, including our experimental data, shows an important kerma rate enhancement at the surface of the tissue, mainly due to the presence of (33)S.

Optimizing binary phase and amplitude filters for PCE, SNR, and discrimination

NASA Technical Reports Server (NTRS)

Downie, John D.

1992-01-01

Binary phase-only filters (BPOFs) have generated much study because of their implementation on currently available spatial light modulator devices. On polarization-rotating devices such as the magneto-optic spatial light modulator (SLM), it is also possible to encode binary amplitude information into two SLM transmission states, in addition to the binary phase information. This is done by varying the rotation angle of the polarization analyzer following the SLM in the optical train. Through this parameter, a continuum of filters may be designed that span the space of binary phase and amplitude filters (BPAFs) between BPOFs and binary amplitude filters. In this study, we investigate the design of optimal BPAFs for the key correlation characteristics of peak sharpness (through the peak-to-correlation energy (PCE) metric), signal-to-noise ratio (SNR), and discrimination between in-class and out-of-class images. We present simulation results illustrating improvements obtained over conventional BPOFs, and trade-offs between the different performance criteria in terms of the filter design parameter.

Optimal 2D-SIM reconstruction by two filtering steps with Richardson-Lucy deconvolution.

PubMed

Perez, Victor; Chang, Bo-Jui; Stelzer, Ernst Hans Karl

2016-11-16

Structured illumination microscopy relies on reconstruction algorithms to yield super-resolution images. Artifacts can arise in the reconstruction and affect the image quality. Current reconstruction methods involve a parametrized apodization function and a Wiener filter. Empirically tuning the parameters in these functions can minimize artifacts, but such an approach is subjective and produces volatile results. We present a robust and objective method that yields optimal results by two straightforward filtering steps with Richardson-Lucy-based deconvolutions. We provide a resource to identify artifacts in 2D-SIM images by analyzing two main reasons for artifacts, out-of-focus background and a fluctuating reconstruction spectrum. We show how the filtering steps improve images of test specimens, microtubules, yeast and mammalian cells.

Optimal 2D-SIM reconstruction by two filtering steps with Richardson-Lucy deconvolution

NASA Astrophysics Data System (ADS)

Perez, Victor; Chang, Bo-Jui; Stelzer, Ernst Hans Karl

2016-11-01

Structured illumination microscopy relies on reconstruction algorithms to yield super-resolution images. Artifacts can arise in the reconstruction and affect the image quality. Current reconstruction methods involve a parametrized apodization function and a Wiener filter. Empirically tuning the parameters in these functions can minimize artifacts, but such an approach is subjective and produces volatile results. We present a robust and objective method that yields optimal results by two straightforward filtering steps with Richardson-Lucy-based deconvolutions. We provide a resource to identify artifacts in 2D-SIM images by analyzing two main reasons for artifacts, out-of-focus background and a fluctuating reconstruction spectrum. We show how the filtering steps improve images of test specimens, microtubules, yeast and mammalian cells.

Fixed-frequency and Frequency-agile (au, HTS) Microstrip Bandstop Filters for L-band Applications

NASA Technical Reports Server (NTRS)

Saenz, Eileen M.; Subramanyam, Guru; VanKeuls, Fred W.; Chen, Chonglin; Miranda, Felix A.

2001-01-01

In this work, we report on the performance of a highly selective, compact 1.83 x 2.08 cm(exp 2) (approx. 0.72 x 0.82 in(exp 2) microstrip line bandstop filter of YBa2CU3O(7-delta) (YBCO) on LaAlO3 (LAO) substrate. The filter is designed for a center frequency of 1.623 GHz for a bandwidth at 3 dB from reference baseline of less than 5.15 MHz, and a bandstop rejection of 30 dB or better. The design and optimization of the filter was performed using Zeland's IE3D circuit simulator. The optimized design was used to fabricate gold (Au) and High-Temperature Superconductor (HTS) versions of the filter. We have also studied an electronically tunable version of the same filter. Tunability of the bandstop characteristics is achieved by the integration of a thin film conductor (Au or HTS) and the nonlinear dielectric ferroelectric SrTiO3 in a conductor/ferroelectric/dielectric modified microstrip configuration. The performance of these filters and comparison with the simulated data will be presented.

Approximation of optimal filter for Ornstein-Uhlenbeck process with quantised discrete-time observation

NASA Astrophysics Data System (ADS)

Bania, Piotr; Baranowski, Jerzy

2018-02-01

Quantisation of signals is a ubiquitous property of digital processing. In many cases, it introduces significant difficulties in state estimation and in consequence control. Popular approaches either do not address properly the problem of system disturbances or lead to biased estimates. Our intention was to find a method for state estimation for stochastic systems with quantised and discrete observation, that is free of the mentioned drawbacks. We have formulated a general form of the optimal filter derived by a solution of Fokker-Planck equation. We then propose the approximation method based on Galerkin projections. We illustrate the approach for the Ornstein-Uhlenbeck process, and derive analytic formulae for the approximated optimal filter, also extending the results for the variant with control. Operation is illustrated with numerical experiments and compared with classical discrete-continuous Kalman filter. Results of comparison are substantially in favour of our approach, with over 20 times lower mean squared error. The proposed filter is especially effective for signal amplitudes comparable to the quantisation thresholds. Additionally, it was observed that for high order of approximation, state estimate is very close to the true process value. The results open the possibilities of further analysis, especially for more complex processes.

Optimizing spatial patterns with sparse filter bands for motor-imagery based brain-computer interface.

PubMed

Zhang, Yu; Zhou, Guoxu; Jin, Jing; Wang, Xingyu; Cichocki, Andrzej

2015-11-30

Common spatial pattern (CSP) has been most popularly applied to motor-imagery (MI) feature extraction for classification in brain-computer interface (BCI) application. Successful application of CSP depends on the filter band selection to a large degree. However, the most proper band is typically subject-specific and can hardly be determined manually. This study proposes a sparse filter band common spatial pattern (SFBCSP) for optimizing the spatial patterns. SFBCSP estimates CSP features on multiple signals that are filtered from raw EEG data at a set of overlapping bands. The filter bands that result in significant CSP features are then selected in a supervised way by exploiting sparse regression. A support vector machine (SVM) is implemented on the selected features for MI classification. Two public EEG datasets (BCI Competition III dataset IVa and BCI Competition IV IIb) are used to validate the proposed SFBCSP method. Experimental results demonstrate that SFBCSP help improve the classification performance of MI. The optimized spatial patterns by SFBCSP give overall better MI classification accuracy in comparison with several competing methods. The proposed SFBCSP is a potential method for improving the performance of MI-based BCI. Copyright © 2015 Elsevier B.V. All rights reserved.

Example-based human motion denoising.

PubMed

Lou, Hui; Chai, Jinxiang

2010-01-01

With the proliferation of motion capture data, interest in removing noise and outliers from motion capture data has increased. In this paper, we introduce an efficient human motion denoising technique for the simultaneous removal of noise and outliers from input human motion data. The key idea of our approach is to learn a series of filter bases from precaptured motion data and use them along with robust statistics techniques to filter noisy motion data. Mathematically, we formulate the motion denoising process in a nonlinear optimization framework. The objective function measures the distance between the noisy input and the filtered motion in addition to how well the filtered motion preserves spatial-temporal patterns embedded in captured human motion data. Optimizing the objective function produces an optimal filtered motion that keeps spatial-temporal patterns in captured motion data. We also extend the algorithm to fill in the missing values in input motion data. We demonstrate the effectiveness of our system by experimenting with both real and simulated motion data. We also show the superior performance of our algorithm by comparing it with three baseline algorithms and to those in state-of-art motion capture data processing software such as Vicon Blade.

Adaptive filtering in biological signal processing.

PubMed

Iyer, V K; Ploysongsang, Y; Ramamoorthy, P A

1990-01-01

The high dependence of conventional optimal filtering methods on the a priori knowledge of the signal and noise statistics render them ineffective in dealing with signals whose statistics cannot be predetermined accurately. Adaptive filtering methods offer a better alternative, since the a priori knowledge of statistics is less critical, real time processing is possible, and the computations are less expensive for this approach. Adaptive filtering methods compute the filter coefficients "on-line", converging to the optimal values in the least-mean square (LMS) error sense. Adaptive filtering is therefore apt for dealing with the "unknown" statistics situation and has been applied extensively in areas like communication, speech, radar, sonar, seismology, and biological signal processing and analysis for channel equalization, interference and echo canceling, line enhancement, signal detection, system identification, spectral analysis, beamforming, modeling, control, etc. In this review article adaptive filtering in the context of biological signals is reviewed. An intuitive approach to the underlying theory of adaptive filters and its applicability are presented. Applications of the principles in biological signal processing are discussed in a manner that brings out the key ideas involved. Current and potential future directions in adaptive biological signal processing are also discussed.

Fourier Spectral Filter Array for Optimal Multispectral Imaging.

PubMed

Jia, Jie; Barnard, Kenneth J; Hirakawa, Keigo

2016-04-01

Limitations to existing multispectral imaging modalities include speed, cost, range, spatial resolution, and application-specific system designs that lack versatility of the hyperspectral imaging modalities. In this paper, we propose a novel general-purpose single-shot passive multispectral imaging modality. Central to this design is a new type of spectral filter array (SFA) based not on the notion of spatially multiplexing narrowband filters, but instead aimed at enabling single-shot Fourier transform spectroscopy. We refer to this new SFA pattern as Fourier SFA, and we prove that this design solves the problem of optimally sampling the hyperspectral image data.

Liquid Li based neutron source for BNCT and science application.

PubMed

Horiike, H; Murata, I; Iida, T; Yoshihashi, S; Hoashi, E; Kato, I; Hashimoto, N; Kuri, S; Oshiro, S

2015-12-01

Liquid lithium (Li) is a candidate material for a target of intense neutron source, heat transfer medium in space engines and charges stripper. For a medical application of BNCT, epithermal neutrons with least energetic neutrons and γ-ray are required so as to avoid unnecessary doses to a patient. This is enabled by lithium target irradiated by protons at 2.5 MeV range, with utilizing the threshold reaction of (7)Li(p,n)(7)Be at 1.88 MeV. In the system, protons at 2.5 MeV penetrate into Li layer by 0.25 mm with dissipating heat load near the surface. To handle it, thin film flow of high velocity is important for stable operation. For the proton accelerator, electrostatic type of the Schnkel or the tandem is planned to be employed. Neutrons generated at 0.6 MeV are gently moderated to epithermal energy while suppressing accompanying γ-ray minimum by the dedicated moderator assembly. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

PubMed

Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

2015-03-01

An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-03-01

New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of MCNP simulated gamma spectra of CdTe detectors for boron neutron capture therapy.

PubMed

Winkler, Alexander; Koivunoro, Hanna; Savolainen, Sauli

2017-06-01

The next step in the boron neutron capture therapy (BNCT) is the real time imaging of the boron concentration in healthy and tumor tissue. Monte Carlo simulations are employed to predict the detector response required to realize single-photon emission computed tomography in BNCT, but have failed to correctly resemble measured data for cadmium telluride detectors. In this study we have tested the gamma production cross-section data tables of commonly used libraries in the Monte Carlo code MCNP in comparison to measurements. The cross section data table TENDL-2008-ACE is reproducing measured data best, whilst the commonly used ENDL92 and other studied libraries do not include correct tables for the gamma production from the cadmium neutron capture reaction that is occurring inside the detector. Furthermore, we have discussed the size of the annihilation peaks of spectra obtained by cadmium telluride and germanium detectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Boron concentration measurements by alpha spectrometry and quantitative neutron autoradiography in cells and tissues treated with different boronated formulations and administration protocols.

PubMed

Bortolussi, Silva; Ciani, Laura; Postuma, Ian; Protti, Nicoletta; Luca Reversi; Bruschi, Piero; Ferrari, Cinzia; Cansolino, Laura; Panza, Luigi; Ristori, Sandra; Altieri, Saverio

2014-06-01

The possibility to measure boron concentration with high precision in tissues that will be irradiated represents a fundamental step for a safe and effective BNCT treatment. In Pavia, two techniques have been used for this purpose, a quantitative method based on charged particles spectrometry and a boron biodistribution imaging based on neutron autoradiography. A quantitative method to determine boron concentration by neutron autoradiography has been recently set-up and calibrated for the measurement of biological samples, both solid and liquid, in the frame of the feasibility study of BNCT. This technique was calibrated and the obtained results were cross checked with those of α spectrometry, in order to validate them. The comparisons were performed using tissues taken form animals treated with different boron administration protocols. Subsequently the quantitative neutron autoradiography was employed to measure osteosarcoma cell samples treated with BPA and with new boronated formulations. © 2013 Published by Elsevier Ltd.

Dose masking feature for BNCT radiotherapy planning

DOEpatents

Cook, Jeremy L.; Wessol, Daniel E.; Wheeler, Floyd J.

2000-01-01

A system for displaying an accurate model of isodoses to be used in radiotherapy so that appropriate planning can be performed prior to actual treatment on a patient. The nature of the simulation of the radiotherapy planning for BNCT and Fast Neutron Therapy, etc., requires that the doses be computed in the entire volume. The "entire volume" includes the patient and beam geometries as well as the air spaces in between. Isodoses derived from the computed doses will therefore extend into the air regions between the patient and beam geometries and thus depict the unrealistic possibility that radiation deposition occurs in regions containing no physical media. This problem is solved by computing the doses for the entire geometry and then masking the physical and air regions along with the isodose contours superimposed over the patient image at the corresponding plane. The user is thus able to mask out (remove) the contour lines from the unwanted areas of the image by selecting the appropriate contour masking region from the raster image.

EMG prediction from Motor Cortical Recordings via a Non-Negative Point Process Filter

PubMed Central

Nazarpour, Kianoush; Ethier, Christian; Paninski, Liam; Rebesco, James M.; Miall, R. Chris; Miller, Lee E.

2012-01-01

A constrained point process filtering mechanism for prediction of electromyogram (EMG) signals from multi-channel neural spike recordings is proposed here. Filters from the Kalman family are inherently sub-optimal in dealing with non-Gaussian observations, or a state evolution that deviates from the Gaussianity assumption. To address these limitations, we modeled the non-Gaussian neural spike train observations by using a generalized linear model (GLM) that encapsulates covariates of neural activity, including the neurons’ own spiking history, concurrent ensemble activity, and extrinsic covariates (EMG signals). In order to predict the envelopes of EMGs, we reformulated the Kalman filter (KF) in an optimization framework and utilized a non-negativity constraint. This structure characterizes the non-linear correspondence between neural activity and EMG signals reasonably. The EMGs were recorded from twelve forearm and hand muscles of a behaving monkey during a grip-force task. For the case of limited training data, the constrained point process filter improved the prediction accuracy when compared to a conventional Wiener cascade filter (a linear causal filter followed by a static non-linearity) for different bin sizes and delays between input spikes and EMG output. For longer training data sets, results of the proposed filter and that of the Wiener cascade filter were comparable. PMID:21659018

Designing manufacturable filters for a 16-band plenoptic camera using differential evolution

NASA Astrophysics Data System (ADS)

Doster, Timothy; Olson, Colin C.; Fleet, Erin; Yetzbacher, Michael; Kanaev, Andrey; Lebow, Paul; Leathers, Robert

2017-05-01

A 16-band plenoptic camera allows for the rapid exchange of filter sets via a 4x4 filter array on the lens's front aperture. This ability to change out filters allows for an operator to quickly adapt to different locales or threat intelligence. Typically, such a system incorporates a default set of 16 equally spaced at-topped filters. Knowing the operating theater or the likely targets of interest it becomes advantageous to tune the filters. We propose using a modified beta distribution to parameterize the different possible filters and differential evolution (DE) to search over the space of possible filter designs. The modified beta distribution allows us to jointly optimize the width, taper and wavelength center of each single- or multi-pass filter in the set over a number of evolutionary steps. Further, by constraining the function parameters we can develop solutions which are not just theoretical but manufacturable. We examine two independent tasks: general spectral sensing and target detection. In the general spectral sensing task we utilize the theory of compressive sensing (CS) and find filters that generate codings which minimize the CS reconstruction error based on a fixed spectral dictionary of endmembers. For the target detection task and a set of known targets, we train the filters to optimize the separation of the background and target signature. We compare our results to the default 16 at-topped non-overlapping filter set which comes with the plenoptic camera and full hyperspectral resolution data which was previously acquired.

Automatic x-ray image contrast enhancement based on parameter auto-optimization.

PubMed

Qiu, Jianfeng; Harold Li, H; Zhang, Tiezhi; Ma, Fangfang; Yang, Deshan

2017-11-01

Insufficient image contrast associated with radiation therapy daily setup x-ray images could negatively affect accurate patient treatment setup. We developed a method to perform automatic and user-independent contrast enhancement on 2D kilo voltage (kV) and megavoltage (MV) x-ray images. The goal was to provide tissue contrast optimized for each treatment site in order to support accurate patient daily treatment setup and the subsequent offline review. The proposed method processes the 2D x-ray images with an optimized image processing filter chain, which consists of a noise reduction filter and a high-pass filter followed by a contrast limited adaptive histogram equalization (CLAHE) filter. The most important innovation is to optimize the image processing parameters automatically to determine the required image contrast settings per disease site and imaging modality. Three major parameters controlling the image processing chain, i.e., the Gaussian smoothing weighting factor for the high-pass filter, the block size, and the clip limiting parameter for the CLAHE filter, were determined automatically using an interior-point constrained optimization algorithm. Fifty-two kV and MV x-ray images were included in this study. The results were manually evaluated and ranked with scores from 1 (worst, unacceptable) to 5 (significantly better than adequate and visually praise worthy) by physicians and physicists. The average scores for the images processed by the proposed method, the CLAHE, and the best window-level adjustment were 3.92, 2.83, and 2.27, respectively. The percentage of the processed images received a score of 5 were 48, 29, and 18%, respectively. The proposed method is able to outperform the standard image contrast adjustment procedures that are currently used in the commercial clinical systems. When the proposed method is implemented in the clinical systems as an automatic image processing filter, it could be useful for allowing quicker and potentially more accurate treatment setup and facilitating the subsequent offline review and verification. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Optimality problem of network topology in stocks market analysis

NASA Astrophysics Data System (ADS)

Djauhari, Maman Abdurachman; Gan, Siew Lee

2015-02-01

Since its introduction fifteen years ago, minimal spanning tree has become an indispensible tool in econophysics. It is to filter the important economic information contained in a complex system of financial markets' commodities. Here we show that, in general, that tool is not optimal in terms of topological properties. Consequently, the economic interpretation of the filtered information might be misleading. To overcome that non-optimality problem, a set of criteria and a selection procedure of an optimal minimal spanning tree will be developed. By using New York Stock Exchange data, the advantages of the proposed method will be illustrated in terms of the power-law of degree distribution.

Ultranarrow bandwidth spectral filtering for long-range free-space quantum key distribution at daytime.

PubMed

Höckel, David; Koch, Lars; Martin, Eugen; Benson, Oliver

2009-10-15

We describe a Fabry-Perot-based spectral filter for free-space quantum key distribution (QKD). A multipass etalon filter was built, and its performance was studied. The whole filter setup was carefully optimized to add less than 2 dB attenuation to a signal beam but block stray light by 21 dB. Simulations show that such a filter might be sufficient to allow QKD satellite downlinks during daytime with the current technology.

Principal Component Noise Filtering for NAST-I Radiometric Calibration

NASA Technical Reports Server (NTRS)

Tian, Jialin; Smith, William L., Sr.

2011-01-01

The National Polar-orbiting Operational Environmental Satellite System (NPOESS) Airborne Sounder Testbed- Interferometer (NAST-I) instrument is a high-resolution scanning interferometer that measures emitted thermal radiation between 3.3 and 18 microns. The NAST-I radiometric calibration is achieved using internal blackbody calibration references at ambient and hot temperatures. In this paper, we introduce a refined calibration technique that utilizes a principal component (PC) noise filter to compensate for instrument distortions and artifacts, therefore, further improve the absolute radiometric calibration accuracy. To test the procedure and estimate the PC filter noise performance, we form dependent and independent test samples using odd and even sets of blackbody spectra. To determine the optimal number of eigenvectors, the PC filter algorithm is applied to both dependent and independent blackbody spectra with a varying number of eigenvectors. The optimal number of PCs is selected so that the total root-mean-square (RMS) error is minimized. To estimate the filter noise performance, we examine four different scenarios: apply PC filtering to both dependent and independent datasets, apply PC filtering to dependent calibration data only, apply PC filtering to independent data only, and no PC filters. The independent blackbody radiances are predicted for each case and comparisons are made. The results show significant reduction in noise in the final calibrated radiances with the implementation of the PC filtering algorithm.

Comparison of filtering methods for extracellular gastric slow wave recordings.

PubMed

Paskaranandavadivel, Niranchan; O'Grady, Gregory; Du, Peng; Cheng, Leo K

2013-01-01

Extracellular recordings are used to define gastric slow wave propagation. Signal filtering is a key step in the analysis and interpretation of extracellular slow wave data; however, there is controversy and uncertainty regarding the appropriate filtering settings. This study investigated the effect of various standard filters on the morphology and measurement of extracellular gastric slow waves. Experimental extracellular gastric slow waves were recorded from the serosal surface of the stomach from pigs and humans. Four digital filters: finite impulse response filter (0.05-1 Hz); Savitzky-Golay filter (0-1.98 Hz); Bessel filter (2-100 Hz); and Butterworth filter (5-100 Hz); were applied on extracellular gastric slow wave signals to compare the changes temporally (morphology of the signal) and spectrally (signals in the frequency domain). The extracellular slow wave activity is represented in the frequency domain by a dominant frequency and its associated harmonics in diminishing power. Optimal filters apply cutoff frequencies consistent with the dominant slow wave frequency (3-5 cpm) and main harmonics (up to ≈ 2 Hz). Applying filters with cutoff frequencies above or below the dominant and harmonic frequencies was found to distort or eliminate slow wave signal content. Investigators must be cognizant of these optimal filtering practices when detecting, analyzing, and interpreting extracellular slow wave recordings. The use of frequency domain analysis is important for identifying the dominant and harmonics of the signal of interest. Capturing the dominant frequency and major harmonics of slow wave is crucial for accurate representation of slow wave activity in the time domain. Standardized filter settings should be determined. © 2012 Blackwell Publishing Ltd.

A distributed, dynamic, parallel computational model: the role of noise in velocity storage

PubMed Central

Merfeld, Daniel M.

2012-01-01

Networks of neurons perform complex calculations using distributed, parallel computation, including dynamic “real-time” calculations required for motion control. The brain must combine sensory signals to estimate the motion of body parts using imperfect information from noisy neurons. Models and experiments suggest that the brain sometimes optimally minimizes the influence of noise, although it remains unclear when and precisely how neurons perform such optimal computations. To investigate, we created a model of velocity storage based on a relatively new technique–“particle filtering”–that is both distributed and parallel. It extends existing observer and Kalman filter models of vestibular processing by simulating the observer model many times in parallel with noise added. During simulation, the variance of the particles defining the estimator state is used to compute the particle filter gain. We applied our model to estimate one-dimensional angular velocity during yaw rotation, which yielded estimates for the velocity storage time constant, afferent noise, and perceptual noise that matched experimental data. We also found that the velocity storage time constant was Bayesian optimal by comparing the estimate of our particle filter with the estimate of the Kalman filter, which is optimal. The particle filter demonstrated a reduced velocity storage time constant when afferent noise increased, which mimics what is known about aminoglycoside ablation of semicircular canal hair cells. This model helps bridge the gap between parallel distributed neural computation and systems-level behavioral responses like the vestibuloocular response and perception. PMID:22514288

Optimum color filters for CCD digital cameras

NASA Astrophysics Data System (ADS)

Engelhardt, Kai; Kunz, Rino E.; Seitz, Peter; Brunner, Harald; Knop, Karl

1993-12-01

As part of the ESPRIT II project No. 2103 (MASCOT) a high performance prototype color CCD still video camera was developed. Intended for professional usage such as in the graphic arts, the camera provides a maximum resolution of 3k X 3k full color pixels. A high colorimetric performance was achieved through specially designed dielectric filters and optimized matrixing. The color transformation was obtained by computer simulation of the camera system and non-linear optimization which minimized the perceivable color errors as measured in the 1976 CIELUV uniform color space for a set of about 200 carefully selected test colors. The color filters were designed to allow perfect colorimetric reproduction in principle and at the same time with imperceptible color noise and with special attention to fabrication tolerances. The camera system includes a special real-time digital color processor which carries out the color transformation. The transformation can be selected from a set of sixteen matrices optimized for different illuminants and output devices. Because the actual filter design was based on slightly incorrect data the prototype camera showed a mean colorimetric error of 2.7 j.n.d. (CIELUV) in experiments. Using correct input data in the redesign of the filters, a mean colorimetric error of only 1 j.n.d. (CIELUV) seems to be feasible, implying that it is possible with such an optimized color camera to achieve such a high colorimetric performance that the reproduced colors in an image cannot be distinguished from the original colors in a scene, even in direct comparison.

Signal-to-noise enhancement techniques for quantum cascade absorption spectrometers employing optimal filtering and other approaches

NASA Astrophysics Data System (ADS)

Disselkamp, R. S.; Kelly, J. F.; Sams, R. L.; Anderson, G. A.

Optical feedback to the laser source in tunable diode laser spectroscopy (TDLS) is known to create intensity modulation noise due to elatoning and optical feedback (i.e. multiplicative technical noise) that usually limits spectral signal-to-noise (S/N). The large technical noise often limits absorption spectroscopy to noise floors 100-fold greater than the Poisson shot noise limit due to fluctuations in the laser intensity. The high output powers generated from quantum cascade (QC) lasers, along with their high gain, makes these injection laser systems especially susceptible to technical noise. In this article we discuss a method of using optimal filtering to reduce technical noise. We have observed S/N enhancements ranging from 20% to a factor of 50. The degree to which optimal filtering enhances S/N depends on the similarity between the Fourier components of the technical noise and those of the signal, with lower S/N enhancements observed for more similar Fourier decompositions of the signal and technical noise. We also examine the linearity of optimal filtered spectra in both time and intensity. This was accomplished by creating a synthetic spectrum for the species being studied (CH4, N2O, CO2 and H2O in ambient air) utilizing line positions and linewidths with an assumed Voigt profile from a commercial database (HITRAN). Agreement better than 0.036% in wavenumber and 1.64% in intensity (up to a 260-fold intensity ratio employed) was observed. Our results suggest that rapid ex post facto digital optimal filtering can be used to enhance S/N for routine trace gas detection.

Optimization of adenovirus 40 and 41 recovery from tap water using small disk filters.

PubMed

McMinn, Brian R

2013-11-01

Currently, the U.S. Environmental Protection Agency's Information Collection Rule (ICR) for the primary concentration of viruses from drinking and surface waters uses the 1MDS filter, but a more cost effective option, the NanoCeram® filter, has been shown to recover comparable levels of enterovirus and norovirus from both matrices. In order to achieve the highest viral recoveries, filtration methods require the identification of optimal concentration conditions that are unique for each virus type. This study evaluated the effectiveness of 1MDS and NanoCeram filters in recovering adenovirus (AdV) 40 and 41 from tap water, and optimized two secondary concentration procedures the celite and organic flocculation method. Adjustments in pH were made to both virus elution solutions and sample matrices to determine which resulted in higher virus recovery. Samples were analyzed by quantitative PCR (qPCR) and Most Probable Number (MPN) techniques and AdV recoveries were determined by comparing levels of virus in sample concentrates to that in the initial input. The recovery of adenovirus was highest for samples in unconditioned tap water (pH 8) using the 1MDS filter and celite for secondary concentration. Elution buffer containing 0.1% sodium polyphosphate at pH 10.0 was determined to be most effective overall for both AdV types. Under these conditions, the average recovery for AdV40 and 41 was 49% and 60%, respectively. By optimizing secondary elution steps, AdV recovery from tap water could be improved at least two-fold compared to the currently used methodology. Identification of the optimal concentration conditions for human AdV (HAdV) is important for timely and sensitive detection of these viruses from both surface and drinking waters. Published by Elsevier B.V.

Optimality study of a gust alleviation system for light wing-loading STOL aircraft

NASA Technical Reports Server (NTRS)

Komoda, M.

1976-01-01

An analytical study was made of an optimal gust alleviation system that employs a vertical gust sensor mounted forward of an aircraft's center of gravity. Frequency domain optimization techniques were employed to synthesize the optimal filters that process the corrective signals to the flaps and elevator actuators. Special attention was given to evaluating the effectiveness of lead time, that is, the time by which relative wind sensor information should lead the actual encounter of the gust. The resulting filter is expressed as an implicit function of the prescribed control cost. A numerical example for a light wing loading STOL aircraft is included in which the optimal trade-off between performance and control cost is systematically studied.

CUDA-based acceleration and BPN-assisted automation of bilateral filtering for brain MR image restoration.

PubMed

Chang, Herng-Hua; Chang, Yu-Ning

2017-04-01

Bilateral filters have been substantially exploited in numerous magnetic resonance (MR) image restoration applications for decades. Due to the deficiency of theoretical basis on the filter parameter setting, empirical manipulation with fixed values and noise variance-related adjustments has generally been employed. The outcome of these strategies is usually sensitive to the variation of the brain structures and not all the three parameter values are optimal. This article is in an attempt to investigate the optimal setting of the bilateral filter, from which an accelerated and automated restoration framework is developed. To reduce the computational burden of the bilateral filter, parallel computing with the graphics processing unit (GPU) architecture is first introduced. The NVIDIA Tesla K40c GPU with the compute unified device architecture (CUDA) functionality is specifically utilized to emphasize thread usages and memory resources. To correlate the filter parameters with image characteristics for automation, optimal image texture features are subsequently acquired based on the sequential forward floating selection (SFFS) scheme. Subsequently, the selected features are introduced into the back propagation network (BPN) model for filter parameter estimation. Finally, the k-fold cross validation method is adopted to evaluate the accuracy of the proposed filter parameter prediction framework. A wide variety of T1-weighted brain MR images with various scenarios of noise levels and anatomic structures were utilized to train and validate this new parameter decision system with CUDA-based bilateral filtering. For a common brain MR image volume of 256 × 256 × 256 pixels, the speed-up gain reached 284. Six optimal texture features were acquired and associated with the BPN to establish a "high accuracy" parameter prediction system, which achieved a mean absolute percentage error (MAPE) of 5.6%. Automatic restoration results on 2460 brain MR images received an average relative error in terms of peak signal-to-noise ratio (PSNR) less than 0.1%. In comparison with many state-of-the-art filters, the proposed automation framework with CUDA-based bilateral filtering provided more favorable results both quantitatively and qualitatively. Possessing unique characteristics and demonstrating exceptional performances, the proposed CUDA-based bilateral filter adequately removed random noise in multifarious brain MR images for further study in neurosciences and radiological sciences. It requires no prior knowledge of the noise variance and automatically restores MR images while preserving fine details. The strategy of exploiting the CUDA to accelerate the computation and incorporating texture features into the BPN to completely automate the bilateral filtering process is achievable and validated, from which the best performance is reached. © 2017 American Association of Physicists in Medicine.

The invariant of the stiffness filter function with the weight filter function of the power function form

NASA Astrophysics Data System (ADS)

Shang, Zhen; Sui, Yun-Kang

2012-12-01

Based on the independent, continuous and mapping (ICM) method and homogenization method, a research model is constructed to propose and deduce a theorem and corollary from the invariant between the weight filter function and the corresponding stiffness filter function of the form of power function. The efficiency in searching for optimum solution will be raised via the choice of rational filter functions, so the above mentioned results are very important to the further study of structural topology optimization.

Validation of search filters for identifying pediatric studies in PubMed.

PubMed

Leclercq, Edith; Leeflang, Mariska M G; van Dalen, Elvira C; Kremer, Leontien C M

2013-03-01

To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity, precision, specificity, accuracy, and number needed to read (NNR). An optimal search filter will have a high sensitivity and high precision with a low NNR. In addition to the PubMed Limits: All Child: 0-18 years filter (in May 2012 renamed to PubMed Filter Child: 0-18 years), 6 search filters for identifying studies including children were identified: 3 developed by Kastner et al, 1 developed by BestBets, one by the Child Health Field, and 1 by the Cochrane Childhood Cancer Group. Three search filters (Cochrane Childhood Cancer Group, Child Health Field, and BestBets) had the highest sensitivity (99.3%, 99.5%, and 99.3%, respectively) but a lower precision (64.5%, 68.4%, and 66.6% respectively) compared with the other search filters. Two Kastner search filters had a high precision (93.0% and 93.7%, respectively) but a low sensitivity (58.5% and 44.8%, respectively). They failed to identify many pediatric studies in our datasets. The search terms responsible for false-positive results in the reference dataset were determined. With these data, we developed a new search filter for identifying studies with children in PubMed with an optimal sensitivity (99.5%) and precision (69.0%). Search filters to identify studies including children either have a low sensitivity or a low precision with a high NNR. A new pediatric search filter with a high sensitivity and a low NNR has been developed. Copyright © 2013 Mosby, Inc. All rights reserved.

An iterative sinogram gap-filling method with object- and scanner-dedicated discrete cosine transform (DCT)-domain filters for high resolution PET scanners.

PubMed

Kim, Kwangdon; Lee, Kisung; Lee, Hakjae; Joo, Sungkwan; Kang, Jungwon

2018-01-01

We aimed to develop a gap-filling algorithm, in particular the filter mask design method of the algorithm, which optimizes the filter to the imaging object by an adaptive and iterative process, rather than by manual means. Two numerical phantoms (Shepp-Logan and Jaszczak) were used for sinogram generation. The algorithm works iteratively, not only on the gap-filling iteration but also on the mask generation, to identify the object-dedicated low frequency area in the DCT-domain that is to be preserved. We redefine the low frequency preserving region of the filter mask at every gap-filling iteration, and the region verges on the property of the original image in the DCT domain. The previous DCT2 mask for each phantom case had been manually well optimized, and the results show little difference from the reference image and sinogram. We observed little or no difference between the results of the manually optimized DCT2 algorithm and those of the proposed algorithm. The proposed algorithm works well for various types of scanning object and shows results that compare to those of the manually optimized DCT2 algorithm without perfect or full information of the imaging object.

Stochastic Adaptive Particle Beam Tracker Using Meer Filter Feedback.

DTIC Science & Technology

1986-12-01

breakthrough required in controlling the beam location. In 1983, Zicker (27] conducted a feasibility study of a simple proportional gain controller... Zicker synthesized his stochastic controller designs from a deterministic optimal LQ controller assuming full state feedback. An LQ controller is a...34Merge" Method 2.5 Simlifying the eer Filter a Zicker ran a performance analysis on the Meer filter and found the Meer filter virtually insensitive to

Ridge filter design and optimization for the broad-beam three-dimensional irradiation system for heavy-ion radiotherapy.

PubMed

Schaffner, B; Kanai, T; Futami, Y; Shimbo, M; Urakabe, E

2000-04-01

The broad-beam three-dimensional irradiation system under development at National Institute of Radiological Sciences (NIRS) requires a small ridge filter to spread the initially monoenergetic heavy-ion beam to a small spread-out Bragg peak (SOBP). A large SOBP covering the target volume is then achieved by a superposition of differently weighted and displaced small SOBPs. Two approaches were studied for the definition of a suitable ridge filter and experimental verifications were performed. Both approaches show a good agreement between the calculated and measured dose and lead to a good homogeneity of the biological dose in the target. However, the ridge filter design that produces a Gaussian-shaped spectrum of the particle ranges was found to be more robust to small errors and uncertainties in the beam application. Furthermore, an optimization procedure for two fields was applied to compensate for the missing dose from the fragmentation tail for the case of a simple-geometry target. The optimized biological dose distributions show that a very good homogeneity is achievable in the target.

Nonlinear Motion Cueing Algorithm: Filtering at Pilot Station and Development of the Nonlinear Optimal Filters for Pitch and Roll

NASA Technical Reports Server (NTRS)

Zaychik, Kirill B.; Cardullo, Frank M.

2012-01-01

Telban and Cardullo have developed and successfully implemented the non-linear optimal motion cueing algorithm at the Visual Motion Simulator (VMS) at the NASA Langley Research Center in 2005. The latest version of the non-linear algorithm performed filtering of motion cues in all degrees-of-freedom except for pitch and roll. This manuscript describes the development and implementation of the non-linear optimal motion cueing algorithm for the pitch and roll degrees of freedom. Presented results indicate improved cues in the specified channels as compared to the original design. To further advance motion cueing in general, this manuscript describes modifications to the existing algorithm, which allow for filtering at the location of the pilot's head as opposed to the centroid of the motion platform. The rational for such modification to the cueing algorithms is that the location of the pilot's vestibular system must be taken into account as opposed to the off-set of the centroid of the cockpit relative to the center of rotation alone. Results provided in this report suggest improved performance of the motion cueing algorithm.

Advanced texture filtering: a versatile framework for reconstructing multi-dimensional image data on heterogeneous architectures

NASA Astrophysics Data System (ADS)

Zellmann, Stefan; Percan, Yvonne; Lang, Ulrich

2015-01-01

Reconstruction of 2-d image primitives or of 3-d volumetric primitives is one of the most common operations performed by the rendering components of modern visualization systems. Because this operation is often aided by GPUs, reconstruction is typically restricted to first-order interpolation. With the advent of in situ visualization, the assumption that rendering algorithms are in general executed on GPUs is however no longer adequate. We thus propose a framework that provides versatile texture filtering capabilities: up to third-order reconstruction using various types of cubic filtering and interpolation primitives; cache-optimized algorithms that integrate seamlessly with GPGPU rendering or with software rendering that was optimized for cache-friendly "Structure of Array" (SoA) access patterns; a memory management layer (MML) that gracefully hides the complexities of extra data copies necessary for memory access optimizations such as swizzling, for rendering on GPGPUs, or for reconstruction schemes that rely on pre-filtered data arrays. We prove the effectiveness of our software architecture by integrating it into and validating it using the open source direct volume rendering (DVR) software DeskVOX.

High-performance information search filters for acute kidney injury content in PubMed, Ovid Medline and Embase.

PubMed

Hildebrand, Ainslie M; Iansavichus, Arthur V; Haynes, R Brian; Wilczynski, Nancy L; Mehta, Ravindra L; Parikh, Chirag R; Garg, Amit X

2014-04-01

We frequently fail to identify articles relevant to the subject of acute kidney injury (AKI) when searching the large bibliographic databases such as PubMed, Ovid Medline or Embase. To address this issue, we used computer automation to create information search filters to better identify articles relevant to AKI in these databases. We first manually reviewed a sample of 22 992 full-text articles and used prespecified criteria to determine whether each article contained AKI content or not. In the development phase (two-thirds of the sample), we developed and tested the performance of >1.3-million unique filters. Filters with high sensitivity and high specificity for the identification of AKI articles were then retested in the validation phase (remaining third of the sample). We succeeded in developing and validating high-performance AKI search filters for each bibliographic database with sensitivities and specificities in excess of 90%. Filters optimized for sensitivity reached at least 97.2% sensitivity, and filters optimized for specificity reached at least 99.5% specificity. The filters were complex; for example one PubMed filter included >140 terms used in combination, including 'acute kidney injury', 'tubular necrosis', 'azotemia' and 'ischemic injury'. In proof-of-concept searches, physicians found more articles relevant to topics in AKI with the use of the filters. PubMed, Ovid Medline and Embase can be filtered for articles relevant to AKI in a reliable manner. These high-performance information filters are now available online and can be used to better identify AKI content in large bibliographic databases.

An optimal modification of a Kalman filter for time scales

NASA Technical Reports Server (NTRS)

Greenhall, C. A.

2003-01-01

The Kalman filter in question, which was implemented in the time scale algorithm TA(NIST), produces time scales with poor short-term stability. A simple modification of the error covariance matrix allows the filter to produce time scales with good stability at all averaging times, as verified by simulations of clock ensembles.

Optimal design of a bank of spatio-temporal filters for EEG signal classification.

PubMed

Higashi, Hiroshi; Tanaka, Toshihisa

2011-01-01

The spatial weights for electrodes called common spatial pattern (CSP) are known to be effective in EEG signal classification for motor imagery based brain computer interfaces (MI-BCI). To achieve accurate classification in CSP, the frequency filter should be properly designed. To this end, several methods for designing the filter have been proposed. However, the existing methods cannot consider plural brain activities described with different frequency bands and different spatial patterns such as activities of mu and beta rhythms. In order to efficiently extract these brain activities, we propose a method to design plural filters and spatial weights which extract desired brain activity. The proposed method designs finite impulse response (FIR) filters and the associated spatial weights by optimization of an objective function which is a natural extension of CSP. Moreover, we show by a classification experiment that the bank of FIR filters which are designed by introducing an orthogonality into the objective function can extract good discriminative features. Moreover, the experiment result suggests that the proposed method can automatically detect and extract brain activities related to motor imagery.

Kalman filter based control for Adaptive Optics

NASA Astrophysics Data System (ADS)

Petit, Cyril; Quiros-Pacheco, Fernando; Conan, Jean-Marc; Kulcsár, Caroline; Raynaud, Henri-François; Fusco, Thierry

2004-12-01

Classical Adaptive Optics suffer from a limitation of the corrected Field Of View. This drawback has lead to the development of MultiConjugated Adaptive Optics. While the first MCAO experimental set-ups are presently under construction, little attention has been paid to the control loop. This is however a key element in the optimization process especially for MCAO systems. Different approaches have been proposed in recent articles for astronomical applications : simple integrator, Optimized Modal Gain Integrator and Kalman filtering. We study here Kalman filtering which seems a very promising solution. Following the work of Brice Leroux, we focus on a frequential characterization of kalman filters, computing a transfer matrix. The result brings much information about their behaviour and allows comparisons with classical controllers. It also appears that straightforward improvements of the system models can lead to static aberrations and vibrations filtering. Simulation results are proposed and analysed thanks to our frequential characterization. Related problems such as model errors, aliasing effect reduction or experimental implementation and testing of Kalman filter control loop on a simplified MCAO experimental set-up could be then discussed.

Robust extrema features for time-series data analysis.

PubMed

Vemulapalli, Pramod K; Monga, Vishal; Brennan, Sean N

2013-06-01

The extraction of robust features for comparing and analyzing time series is a fundamentally important problem. Research efforts in this area encompass dimensionality reduction using popular signal analysis tools such as the discrete Fourier and wavelet transforms, various distance metrics, and the extraction of interest points from time series. Recently, extrema features for analysis of time-series data have assumed increasing significance because of their natural robustness under a variety of practical distortions, their economy of representation, and their computational benefits. Invariably, the process of encoding extrema features is preceded by filtering of the time series with an intuitively motivated filter (e.g., for smoothing), and subsequent thresholding to identify robust extrema. We define the properties of robustness, uniqueness, and cardinality as a means to identify the design choices available in each step of the feature generation process. Unlike existing methods, which utilize filters "inspired" from either domain knowledge or intuition, we explicitly optimize the filter based on training time series to optimize robustness of the extracted extrema features. We demonstrate further that the underlying filter optimization problem reduces to an eigenvalue problem and has a tractable solution. An encoding technique that enhances control over cardinality and uniqueness is also presented. Experimental results obtained for the problem of time series subsequence matching establish the merits of the proposed algorithm.

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

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

Farías, R. O.; Trivillin, V. A.; Portu, A. M.

Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (L)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Twomore » kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.« less

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina.

PubMed

Farías, R O; Garabalino, M A; Ferraris, S; Santa María, J; Rovati, O; Lange, F; Trivillin, V A; Monti Hughes, A; Pozzi, E C C; Thorp, S I; Curotto, P; Miller, M E; Santa Cruz, G A; Bortolussi, S; Altieri, S; Portu, A M; Saint Martin, G; Schwint, A E; González, S J

2015-07-01

Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

Optimization of tungsten x-ray spectra for digital mammography: a comparison of model to experiment

NASA Astrophysics Data System (ADS)

Andre, Michael P.; Spivey, Brett A.

1997-05-01

Tungsten (W) target x-rays tubes are being studied for use in digital mammography to improve x-ray flux, reduce noise and increase tube heat capacity. A parametric model was developed for digital mammography to evaluate optimization of x-ray spectra for a particular sensor. The model computes spectra and mean glandular doses (MGD) for combinations of W target, beam filters, kVp, breast type and thickness. Two figures of merit were defined: (signal/noise)2/MGD and spectral quantum efficiency; these were computed as a means to approach optimization of object contrast. The model is derived from a combination of classic equations, XCOM from NBS, and published data. X-ray spectra were calculated and measured for filters of Al, Sn, Rh, Mo and Ag on a Eureka tube. (Signal/noise)2/MGD was measured for a filtered W target tube and a digital camera employing CsI scintillator optically coupled to a CCD for which the detective quantum efficiency (DQE) was known. A 3-mm thick acrylic disk was imaged on thickness of 3-8 cm of acrylic and the results were compared to the predictions of the model. The relative error between predicted and measured spectra was +/- 2 percent from 24 to 34 kVp. Calculated MGD as a function of breast thickness, half-value layer and beam filter compares very well to published data. Best performance was found for the following combinations: Mo filter with 30 mm breast, Ag filter with 45 mm, Sn filter for 60 mm, and Al filter for 75 mm thick breast. The parametric model agrees well with measurement and provides a means to explore optimum combinations of kVp and beam filter. For a particular detector, this data may be used with the DQE to estimate total system signal-to-noise ratio for a particular imaging task.

How to find and type red/brown dwarf stars in near-infrared imaging space observatories

NASA Astrophysics Data System (ADS)

Willemn Holwerda, Benne; Ryan, Russell; Bridge, Joanna; Pirzkal, Nor; Kenworthy, Matthew; Andersen, Morten; Wilkins, Stephen; Trenti, Michele; Meshkat, Tiffany; Bernard, Stephanie; Smit, Renske

2018-01-01

Here we evaluate the near-infrared colors of brown dwarfs as observed with four major infrared imaging space observatories: the Hubble Space Telescope (HST), the James Webb Space Telescope (JWST), the EUCLID mission, and the WFIRST telescope. We use the splat ISPEX spectroscopic library to map out the colors of the M, L, and T-type brown dwarfs. We identify which color-color combination is optimal for identifying broad type and which single color is optimal to then identify the subtype (e.g., T0-9). We evaluate each observatory separately as well as the the narrow-field (HST and JWST) and wide-field (EULID and WFIRST) combinations.HST filters used thus far for high-redshift searches (e.g. CANDELS and BoRG) are close to optimal within the available filter combinations. A clear improvement over HST is one of two broad/medium filter combinations on JWST: pairing F140M with either F150W or F162M discriminates well between brown dwarf subtypes. The improvement of JWST the filter set over the HST one is so marked that any combination of HST and JWST filters does not improve the classification.The EUCLID filter set alone performs poorly in terms of typing brown dwarfs and WFIRST performs only marginally better, despite a wider selection of filters. A combined EUCLID and WFIRST observation, using WFIRST's W146 and F062 and EUCLID's Y-band, allows for a much better discrimination between broad brown dwarf categories. In this respect, WFIRST acts as a targeted follow-up observatory for the all-sky EUCLID survey. However, subsequent subtyping with the combination of EUCLID and WFIRST observations remains uncertain due to the lack of medium or narrow-band filters in this wavelength range. We argue that a medium band added to the WFIRST filter selection would greatly improve its ability to preselect against brown dwarfs in high-latitude surveys.

Development of genetic algorithm-based optimization module in WHAT system for hydrograph analysis and model application

NASA Astrophysics Data System (ADS)

Lim, Kyoung Jae; Park, Youn Shik; Kim, Jonggun; Shin, Yong-Chul; Kim, Nam Won; Kim, Seong Joon; Jeon, Ji-Hong; Engel, Bernard A.

2010-07-01

Many hydrologic and water quality computer models have been developed and applied to assess hydrologic and water quality impacts of land use changes. These models are typically calibrated and validated prior to their application. The Long-Term Hydrologic Impact Assessment (L-THIA) model was applied to the Little Eagle Creek (LEC) watershed and compared with the filtered direct runoff using BFLOW and the Eckhardt digital filter (with a default BFI max value of 0.80 and filter parameter value of 0.98), both available in the Web GIS-based Hydrograph Analysis Tool, called WHAT. The R2 value and the Nash-Sutcliffe coefficient values were 0.68 and 0.64 with BFLOW, and 0.66 and 0.63 with the Eckhardt digital filter. Although these results indicate that the L-THIA model estimates direct runoff reasonably well, the filtered direct runoff values using BFLOW and Eckhardt digital filter with the default BFI max and filter parameter values do not reflect hydrological and hydrogeological situations in the LEC watershed. Thus, a BFI max GA-Analyzer module (BFI max Genetic Algorithm-Analyzer module) was developed and integrated into the WHAT system for determination of the optimum BFI max parameter and filter parameter of the Eckhardt digital filter. With the automated recession curve analysis method and BFI max GA-Analyzer module of the WHAT system, the optimum BFI max value of 0.491 and filter parameter value of 0.987 were determined for the LEC watershed. The comparison of L-THIA estimates with filtered direct runoff using an optimized BFI max and filter parameter resulted in an R2 value of 0.66 and the Nash-Sutcliffe coefficient value of 0.63. However, L-THIA estimates calibrated with the optimized BFI max and filter parameter increased by 33% and estimated NPS pollutant loadings increased by more than 20%. This indicates L-THIA model direct runoff estimates can be incorrect by 33% and NPS pollutant loading estimation by more than 20%, if the accuracy of the baseflow separation method is not validated for the study watershed prior to model comparison. This study shows the importance of baseflow separation in hydrologic and water quality modeling using the L-THIA model.

Optimal application of Morrison's iterative noise removal for deconvolution. Appendices

NASA Technical Reports Server (NTRS)

Ioup, George E.; Ioup, Juliette W.

1987-01-01

Morrison's iterative method of noise removal, or Morrison's smoothing, is applied in a simulation to noise-added data sets of various noise levels to determine its optimum use. Morrison's smoothing is applied for noise removal alone, and for noise removal prior to deconvolution. For the latter, an accurate method is analyzed to provide confidence in the optimization. The method consists of convolving the data with an inverse filter calculated by taking the inverse discrete Fourier transform of the reciprocal of the transform of the response of the system. Various length filters are calculated for the narrow and wide Gaussian response functions used. Deconvolution of non-noisy data is performed, and the error in each deconvolution calculated. Plots are produced of error versus filter length; and from these plots the most accurate length filters determined. The statistical methodologies employed in the optimizations of Morrison's method are similar. A typical peak-type input is selected and convolved with the two response functions to produce the data sets to be analyzed. Both constant and ordinate-dependent Gaussian distributed noise is added to the data, where the noise levels of the data are characterized by their signal-to-noise ratios. The error measures employed in the optimizations are the L1 and L2 norms. Results of the optimizations for both Gaussians, both noise types, and both norms include figures of optimum iteration number and error improvement versus signal-to-noise ratio, and tables of results. The statistical variation of all quantities considered is also given.

Thermal control design of the Lightning Mapper Sensor narrow-band spectral filter

NASA Technical Reports Server (NTRS)

Flannery, Martin R.; Potter, John; Raab, Jeff R.; Manlief, Scott K.

1992-01-01

The performance of the Lightning Mapper Sensor is dependent on the temperature shifts of its narrowband spectral filter. To perform over a 10 degree FOV with an 0.8 nm bandwidth, the filter must be 15 cm in diameter and mounted externally to the telescope optics. The filter thermal control required a filter design optimized for minimum bandpass shift with temperature, a thermal analysis of substrate materials for maximum temperature uniformity, and a thermal radiation analysis to determine the parameter sensitivity of the radiation shield for the filter, the filter thermal recovery time after occultation, and heater power to maintain filter performance in the earth-staring geosynchronous environment.

Design considerations for near-infrared filter photometry: effects of noise sources and selectivity.

PubMed

Tarumi, Toshiyasu; Amerov, Airat K; Arnold, Mark A; Small, Gary W

2009-06-01

Optimal filter design of two-channel near-infrared filter photometers is investigated for simulated two-component systems consisting of an analyte and a spectrally overlapping interferent. The degree of overlap between the analyte and interferent bands is varied over three levels. The optimal design is obtained for three cases: a source or background flicker noise limited case, a shot noise limited case, and a detector noise limited case. Conventional photometers consist of narrow-band optical filters with their bands located at discrete wavelengths. However, the use of broadband optical filters with overlapping responses has been proposed to obtain as much signal as possible from a weak and broad analyte band typical of near-infrared absorptions. One question regarding the use of broadband optical filters with overlapping responses is the selectivity achieved by such filters. The selectivity of two-channel photometers is evaluated on the basis of the angle between the analyte and interferent vectors in the space spanned by the relative change recorded for each of the two detector channels. This study shows that for the shot noise limited or detector noise limited cases, the slight decrease in selectivity with the use of broadband optical filters can be compensated by the higher signal-to-noise ratio afforded by the use of such filters. For the source noise limited case, the best quantitative results are obtained with the use of narrow-band non-overlapping optical filters.

Sinogram noise reduction for low-dose CT by statistics-based nonlinear filters

NASA Astrophysics Data System (ADS)

Wang, Jing; Lu, Hongbing; Li, Tianfang; Liang, Zhengrong

2005-04-01

Low-dose CT (computed tomography) sinogram data have been shown to be signal-dependent with an analytical relationship between the sample mean and sample variance. Spatially-invariant low-pass linear filters, such as the Butterworth and Hanning filters, could not adequately handle the data noise and statistics-based nonlinear filters may be an alternative choice, in addition to other choices of minimizing cost functions on the noisy data. Anisotropic diffusion filter and nonlinear Gaussian filters chain (NLGC) are two well-known classes of nonlinear filters based on local statistics for the purpose of edge-preserving noise reduction. These two filters can utilize the noise properties of the low-dose CT sinogram for adaptive noise reduction, but can not incorporate signal correlative information for an optimal regularized solution. Our previously-developed Karhunen-Loeve (KL) domain PWLS (penalized weighted least square) minimization considers the signal correlation via the KL strategy and seeks the PWLS cost function minimization for an optimal regularized solution for each KL component, i.e., adaptive to the KL components. This work compared the nonlinear filters with the KL-PWLS framework for low-dose CT application. Furthermore, we investigated the nonlinear filters for post KL-PWLS noise treatment in the sinogram space, where the filters were applied after ramp operation on the KL-PWLS treated sinogram data prior to backprojection operation (for image reconstruction). By both computer simulation and experimental low-dose CT data, the nonlinear filters could not outperform the KL-PWLS framework. The gain of post KL-PWLS edge-preserving noise filtering in the sinogram space is not significant, even the noise has been modulated by the ramp operation.

Optimal filter design with progressive genetic algorithm for local damage detection in rolling bearings

NASA Astrophysics Data System (ADS)

Wodecki, Jacek; Michalak, Anna; Zimroz, Radoslaw

2018-03-01

Harsh industrial conditions present in underground mining cause a lot of difficulties for local damage detection in heavy-duty machinery. For vibration signals one of the most intuitive approaches of obtaining signal with expected properties, such as clearly visible informative features, is prefiltration with appropriately prepared filter. Design of such filter is very broad field of research on its own. In this paper authors propose a novel approach to dedicated optimal filter design using progressive genetic algorithm. Presented method is fully data-driven and requires no prior knowledge of the signal. It has been tested against a set of real and simulated data. Effectiveness of operation has been proven for both healthy and damaged case. Termination criterion for evolution process was developed, and diagnostic decision making feature has been proposed for final result determinance.

Least squares restoration of multichannel images

NASA Technical Reports Server (NTRS)

Galatsanos, Nikolas P.; Katsaggelos, Aggelos K.; Chin, Roland T.; Hillery, Allen D.

1991-01-01

Multichannel restoration using both within- and between-channel deterministic information is considered. A multichannel image is a set of image planes that exhibit cross-plane similarity. Existing optimal restoration filters for single-plane images yield suboptimal results when applied to multichannel images, since between-channel information is not utilized. Multichannel least squares restoration filters are developed using the set theoretic and the constrained optimization approaches. A geometric interpretation of the estimates of both filters is given. Color images (three-channel imagery with red, green, and blue components) are considered. Constraints that capture the within- and between-channel properties of color images are developed. Issues associated with the computation of the two estimates are addressed. A spatially adaptive, multichannel least squares filter that utilizes local within- and between-channel image properties is proposed. Experiments using color images are described.