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1.
Sci Rep ; 12(1): 1484, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087083

RESUMO

Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 107 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/métodos , Radioterapia (Especialidade)/métodos , Radiobiologia/métodos , Linhagem Celular , Humanos , Lasers , Método de Monte Carlo , Radiobiologia/instrumentação , Radiometria/instrumentação , Radiometria/métodos , Dosagem Radioterapêutica , Síncrotrons
2.
Probl Radiac Med Radiobiol ; 25: 10-17, 2020 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-33361827

RESUMO

Research activities and scientific advance achieved in 2019 at the State Institution «National Research Center forRadiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problemsof the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaborationwith the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annualreport. The report presents the results of fundamental and applied research works of the study of radiation effectsand health effects of the Chornobyl accident.The report also shows the results of scientific-organizational and health care work, staff training.The Scientific Council meeting of NAMS approved the NRCRM Annual Report.


Assuntos
Academias e Institutos/história , Acidente Nuclear de Chernobyl , Cooperação Internacional/história , Lesões por Radiação/terapia , Radiobiologia/métodos , Academias e Institutos/organização & administração , Animais , História do Século XX , História do Século XXI , Humanos , Lesões por Radiação/patologia , Radiobiologia/história , Radiobiologia/instrumentação , Radiometria/instrumentação , Radiometria/métodos , Ucrânia
3.
PLoS Biol ; 18(5): e3000669, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32428004

RESUMO

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth's protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the "GCR Simulator" to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%-75%) and helium ions (approximately 10%-20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA's innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.


Assuntos
Radiação Cósmica , Radiobiologia/instrumentação , Simulação de Ambiente Espacial , Animais , Humanos , Camundongos , Ratos , Voo Espacial
4.
Phys Med ; 64: 166-173, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515016

RESUMO

Amongst the scientific frameworks powered by the Monte Carlo (MC) toolkit Geant4 (Agostinelli et al., 2003), the TOPAS (Tool for Particle Simulation) (Perl et al., 2012) is one. TOPAS focuses on providing ease of use, and has significant implementation in the radiation oncology space at present. TOPAS functionality extends across the full capacity of Geant4, is freely available to non-profit users, and is being extended into radiobiology via TOPAS-nBIO (Ramos-Mendez et al., 2018). A current "grand problem" in cancer therapy is to convert the dose of treatment from physical dose to biological dose, optimized ultimately to the individual context of administration of treatment. Biology MC calculations are some of the most complex and require significant computational resources. In order to enhance TOPAS's ability to become a critical tool to explore the definition and application of biological dose in radiation therapy, we chose to explore the use of Field Programmable Gate Array (FPGA) chips to speedup the Geant4 calculations at the heart of TOPAS, because this approach called "Reconfigurable Computing" (RC), has proven able to produce significant (around 90x) (Sajish et al., 2012) speed increases in scientific computing. Here, we describe initial steps to port Geant4 and TOPAS to be used on FPGA. We provide performance analysis of the current TOPAS/Geant4 code from an RC implementation perspective. Baseline benchmarks are presented. Achievable performance figures of the subsections of the code on optimal hardware are presented; Aspects of practical implementation of "Monte Carlo on a chip" are also discussed.


Assuntos
Método de Monte Carlo , Radiobiologia/instrumentação , Planejamento da Radioterapia Assistida por Computador , Fatores de Tempo
5.
Med Phys ; 46(11): 5294-5303, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31461781

RESUMO

PURPOSE: Dose verification in preclinical radiotherapy is often challenged by a lack of standardization in the techniques and technologies commonly employed along with the inherent difficulty of dosimetry associated with small-field kilovoltage sources. As a consequence, the accuracy of dosimetry in radiobiological research has been called into question. Fortunately, the development and characterization of realistic small-animal phantoms has emerged as an effective and accessible means of improving dosimetric accuracy and precision in this context. The application of three-dimensional (3D) printing, in particular, has enabled substantial improvements in the conformity of representative phantoms with respect to the small animals they are modeled after. In this study, our goal was to evaluate a fully 3D printed mouse phantom for use in preclinical treatment verification of sophisticated therapies for various anatomical targets of therapeutic interest. METHODS: An anatomically realistic mouse phantom was 3D printed based on segmented microCT data of a tumor-bearing mouse. The phantom was modified to accommodate both laser-cut EBT3 radiochromic film within the mouse thorax and a plastic scintillator dosimeter (PSD), which may be placed within the brain, abdomen, or 1-cm flank subcutaneous tumor. Various treatments were delivered on an image-guided small-animal irradiator in order to determine the doses to isocenter using a PSD and validate lateral- and depth-dose distributions using film dosimeters. On-board cone-beam CT imaging was used to localize isocenter to the film plane or PSD active element prior to irradiation. The PSD irradiations comprised a 3 × 3 mm2 brain arc, 5 × 5 mm2 parallel-opposed pair (POP), and 5-beam 10 × 10 mm2 abdominal coplanar arrangement while two-dimensional (2D) film dose distributions were acquired using a 3 × 3 mm2 arc and both 5 × 5 and 10 × 10 mm2 3-beam coplanar plans. A validated Monte Carlo (MC) model of the source was used as to verify the accuracy of the film and PSD dose measurements. computer-aided design (CAD) geometries for the mouse phantom and dosimeters were imported directly into the MC code to allow for highly accurate reproduction of the physical experiment conditions. Experimental and MC-derived film data were co-registered and film dose profiles were compared for points above 90% of the dose maximum. Point dose measurements obtained with the PSD were similarly compared for each of the candidate (brain, abdomen, and tumor) treatment sites. RESULTS: For each treatment configuration and anatomical target, the MC-calculated and measured doses met the proposed 5% agreement goal for dose accuracy in radiobiology experiments. The 2D film and MC dose distributions were successfully registered and mean doses for lateral profiles were found to agree to within 2.3% in all cases. Isocentric point-dose measurements taken with the PSD were similarly consistent, with a maximum percentage deviation of 3.2%. CONCLUSIONS: Our study confirms the utility of 3D printed phantom design in providing accurate dose estimates for a variety of preclinical treatment paradigms. As a tool for pretreatment dose verification, the phantom may be of particular interest to researchers for its ability to facilitate precise dosimetry while fostering a reduction in cost for radiobiology experiments.


Assuntos
Imagens de Fantasmas , Impressão Tridimensional , Radiobiologia/instrumentação , Animais , Dosimetria Fotográfica , Camundongos
6.
Phys Med ; 65: 21-28, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430582

RESUMO

The Centre for the Clinical Application of Particles' Laser-hybrid Accelerator for Radiobiological Applications (LhARA) facility is being studied and requires simulation of novel accelerator components (such as the Gabor lens capture system), detector simulation and simulation of the ion beam interaction with cells. The first stage of LhARA will provide protons up to 15 MeV for in vitro studies. The second stage of LhARA will use a fixed-field accelerator to increase the energy of the particles to allow in vivo studies with protons and in vitro studies with heavier ions. BDSIM, a Geant4 based accelerator simulation tool, has been used to perform particle tracking simulations to verify the beam optics design done by BeamOptics and these show good agreement. Design parameters were defined based on an EPOCH simulation of the laser source and a series of mono-energetic input beams were generated from this by BDSIM. The tracking results show the large angular spread of the input beam (0.2 rad) can be transported with a transmission of almost 100% whilst keeping divergence at the end station very low (<0.1 mrad). The legacy of LhARA will be the demonstration of technologies that could drive a step-change in the provision of proton and light ion therapy (i.e. a laser source coupled to a Gabor lens capture and a fixed-field accelerator), and a system capable of delivering a comprehensive set of experimental data that can be used to enhance the clinical application of proton and light ion therapy.


Assuntos
Modelos Teóricos , Radiobiologia/instrumentação , Aceleradores de Partículas
7.
Phys Med Biol ; 64(13): 135013, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31075786

RESUMO

Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician's precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiobiology research. Comparative research of the biological differences between proton and x-ray beams could benefit from an integrated small animal irradiation system for in vivo experiments and corresponding quality assurance (QA) protocols to ensure rigor and reproducibility. The objective of this study is to incorporate a proton beam into a small animal radiotherapy platform while implementing QA modelled after clinical protocols. A 225 kV x-ray small animal radiation research platform (SARRP) was installed on rails to align with a modified proton experimental beamline from a 230 MeV cyclotron-based clinical system. Collimated spread out Bragg peaks (SOBP) were produced with beam parameters compatible with small animal irradiation. Proton beam characteristics were measured and alignment reproducibility with the x-ray system isocenter was evaluated. A QA protocol was designed to ensure consistent proton beam quality and alignment. As a preliminary study, cellular damage via γ-H2AX immunofluorescence staining in an irradiated mouse tumor model was used to verify the beam range in vivo. The beam line was commissioned to deliver Bragg peaks with range 4-30 mm in water at 2 Gy min-1. SOBPs were delivered with width up to 25 mm. Proton beam alignment with the x-ray system agreed within 0.5 mm. A QA phantom was created to ensure reproducible alignment of the platform and verify beam delivery. γ-H2AX staining verified expected proton range in vivo. An image-guided small animal proton/x-ray research system was developed to enable in vivo investigations of radiobiological effects of proton beams, comparative studies between proton and x-ray beams, and investigations into novel proton treatment methods.


Assuntos
Terapia com Prótons/instrumentação , Radiobiologia/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Animais , Desenho de Equipamento , Camundongos , Imagens de Fantasmas , Controle de Qualidade , Reprodutibilidade dos Testes , Síncrotrons
8.
Med Phys ; 46(5): 2356-2362, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30924942

RESUMO

PURPOSE: With the increase in proton therapy centers, there is a growing need to make progress in preclinical proton radiation biology to give accessible data to medical physicists and practicing radiation oncologists. METHODS: A cyclotron usually producing radioisotopes with a proton beam at an energy of about 25 MeV after acceleration, was used for radiobiology studies. Depleted silicon surface barrier detectors were used for the beam energy measurement. A complementary metal oxide semiconductor (CMOS) sensor and a plastic scintillator detector were used for fluence measurement, and compared to Geant4 and an in-house analytical dose modeling developed for this purpose. Also, from the energy measurement of each attenuated beam, the dose-averaged linear energy transfer (LETd ) was calculated with Geant4. RESULTS: The measured proton beam energy was 24.85 ± 0.14 MeV with an energy straggling of 127 ± 22 keV before scattering and extraction in air. The measured flatness was within ± 2.1% over 9 mm in diameter. A wide range of LETd is achievable: constant between the entrance and the exit of the cancer cell sample ranging from 2.2 to 8 keV/µm, beyond 20 keV/µm, and an average of 2-5 keV/µm in a scattering spread-out Bragg peak calculated for an example of a 6-mm-thick xenograft tumor. CONCLUSION: The dosimetry and the characterization of a 25-MeV proton beam line for preclinical radiobiology research was performed by measurements and modeling, demonstrating the feasibility of delivering a proton beam for preclinical in vivo and in vitro studies with LETd of clinical interest.


Assuntos
Prótons , Radiobiologia/instrumentação , Radiometria/instrumentação , Método de Monte Carlo , Doses de Radiação
9.
Radiat Prot Dosimetry ; 183(1-2): 264-269, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726978

RESUMO

Human exposure to α-particles from radon and other radionuclides is associated with carcinogenesis, but if well controlled and targeted to cancer cells, α-particles may be used in radiotherapy. Thus, it is important to understand the biological effects of α-particles to predict cancer risk and optimise radiotherapy. To enable studies of α-particles in cells, we developed and characterised an α-particle automated irradiation rig that allows exposures at a shallow angle (70° to the normal) of cell monolayers in a 30 mm diameter dish to complement standard perpendicular irradiations. The measured incident energy of the α-particles was 3.3 ± 0.5 MeV (LET in water = 120 keV µm-1), with a maximum incident dose rate of 1.28 ± 0.02 Gy min-1, which for a 5 µm cell monolayer corresponds to a mean dose rate of 1.57 ± 0.02 Gy min-1 and a mean LET in water of 154 keV µm-1. The feasibility of resolving radiation-induced DNA double-strand breaks (DSB) foci along the track of α-particles was demonstrated using immunofluorescent labelling with γH2AX and 53BP1 in normal MRC-5 human lung cells.


Assuntos
Partículas alfa , Células Cultivadas/efeitos da radiação , Pulmão/citologia , Radiobiologia/instrumentação , Quebras de DNA de Cadeia Dupla , Desenho de Equipamento , Humanos , Transferência Linear de Energia
10.
Radiat Prot Dosimetry ; 183(1-2): 131-135, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561691

RESUMO

In recent years, several approaches have been proposed to provide an understanding of the enhanced relative biological effectiveness of ion beams based on multi-scale models of their radiation effects. Among these, the BioQuaRT project was the only one which focused on developing metrology for a multi-scale characterization of particle track structure. The progress made within the BioQuaRT project has motivated the formation of a department 'Radiation Effects' at PTB dedicated to metrological research on ionizing radiation effects. This paper gives an overview of the department's present research directions and shortly discusses ideas for the future development of metrology related to biological effects of ion beams that are based on a stakeholder consultation.


Assuntos
Fenômenos Fisiológicos Celulares/efeitos da radiação , Dano ao DNA/efeitos da radiação , Aceleradores de Partículas/instrumentação , Radiobiologia/instrumentação , Relação Dose-Resposta à Radiação , Alemanha , Transferência Linear de Energia , Radiação Ionizante , Eficiência Biológica Relativa
11.
Radiat Prot Dosimetry ; 183(1-2): 274-279, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535406

RESUMO

The recent worldwide spread of Proton Therapy centers paves the way to new opportunities for basic and applied research related to the use of accelerated proton beams. Clinical centers make use of proton beam energies up to about 230 MeV. This represents an interesting energy range for a large spectrum of applications, including detector testing, radiation shielding and space research. Additionally, radiobiology research might benefit for a larger availability of proton beams, especially in those centers where a room dedicated to research activities also exists. Here, we describe the initial activities for the setup of a radiobiology irradiation facility at the Trento Proton Therapy Center. Data referring to the characterization of the beam in air are essential to that purpose and will be presented. A basic setup for large field irradiation will be also proposed, which is needed for the majority of in vitro and in vivo radiobiology experiments.


Assuntos
Terapia com Prótons , Radiobiologia/instrumentação , Desenho de Equipamento , Arquitetura de Instituições de Saúde , Itália , Radiometria , Espalhamento de Radiação
12.
Phys Med Biol ; 63(24): 245022, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30524061

RESUMO

There is increasing interest in using alpha particle emitting radionuclides for cancer therapy because of their unique cytotoxic properties which are advantageous for eradicating tumor cells. The high linear energy transfer (LET) of alpha particles produces a correspondingly high density of ionizations along their track. Alpha particle emitting radiopharmaceuticals deposit this energy in tissues over prolonged periods with complex dose rate patterns that depend on the physical half-life of the radionuclide, and the biological uptake and clearance half-times in tumor and normal tissues. We have previously shown that the dose rate increase half-time that arises as a consequence of these biokinetics can have a profound effect on the radiotoxicity of low-LET radiation. The microcontroller hardware and software described here offer a unique way to deliver these complex dose rate patterns with a broad-beam alpha particle irradiator, thereby enabling experiments to study the radiobiology of complex dose rate patterns of alpha particles. Complex dose rate patterns were created by precise manipulation of the timing of opening and closing of the electromechanical shutters of an α-particle irradiator. An Arduino Uno and custom circuitry was implemented to control the shutters. The software that controls the circuits and shutters has a user-friendly Graphic User Interface (GUI). Alpha particle detectors were used to validate the programmed dose rate profiles. Circuit diagrams and downloadable software are provided to facilitate adoption of this technology by other radiobiology laboratories.


Assuntos
Partículas alfa/uso terapêutico , Transferência Linear de Energia , Neoplasias/radioterapia , Radiobiologia/instrumentação , Compostos Radiofarmacêuticos , Software , Meia-Vida , Humanos , Neoplasias/metabolismo
13.
Radiat Res ; 188(4.2): 470-474, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28723273

RESUMO

Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the presence or absence of low-dose ionizing radiation exposure.


Assuntos
Radiação de Fundo/efeitos adversos , Laboratórios , Exposição à Radiação/efeitos adversos , Radiobiologia/métodos , Animais , Radiação Cósmica/efeitos adversos , Radiobiologia/instrumentação , Salmonidae/embriologia
14.
Semin Radiat Oncol ; 26(4): 349-55, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27619256

RESUMO

There is a growing awareness of the gaps in the technical methods employed in radiation biology experiments. These quality gaps can have a substantial effect on the reliability and reproducibility of results as outlined in several recent meta-studies. This is especially true in the context of the newer laboratory irradiation technologies. These technologies allow for delivery of highly localized dose distributions and increased spatial accuracy but also present increased challenges of their own. In this article, we highlight some of the features of the new technologies and the experiments they support; this includes image-guided localized radiation systems, microirradiator systems using carbon nanotubes and physical radiation modifiers like gold nanoparticles. We discuss the key technical issues related to the consistency and quality of modern radiation biology experiments including dosimetry protocols that are essential to all experiments, quality assurance approaches, methods to validate physical radiation targeting including immunohistochemical assays and other biovalidation approaches. We highlight the future needs in terms of education and training and the creation of tools for cross-institutional benchmarking quality in preclinical studies. The demands for increased experimental rigor are challenging but can be met with an awareness and a systematic approach which ensures quality.


Assuntos
Radiobiologia/instrumentação , Radiobiologia/métodos , Previsões , Ouro , Humanos , Nanopartículas , Nanotubos de Carbono , Radiobiologia/tendências , Radiometria , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem , Reprodutibilidade dos Testes
15.
Cancer Lett ; 371(2): 292-300, 2016 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-26704304

RESUMO

Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists.


Assuntos
Microfluídica/métodos , Neoplasias/radioterapia , Radioterapia (Especialidade)/métodos , Radiobiologia/métodos , Animais , Automação Laboratorial , Biomarcadores Tumorais/metabolismo , Desenho de Equipamento , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Neoplasias/metabolismo , Neoplasias/patologia , Doses de Radiação , Radioterapia (Especialidade)/instrumentação , Radiobiologia/instrumentação
16.
Radiat Prot Dosimetry ; 166(1-4): 182-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25911406

RESUMO

Charged-particle microbeams (CPMs) allow the targeting of sub-cellular compartments with a counted number of energetic ions. While initially developed in the late 1990s to overcome the statistical fluctuation on the number of traversals per cell inevitably associated with broad beam irradiations, CPMs have generated a growing interest and are now used in a wide range of radiation biology studies. Besides the study of the low-dose cellular response that has prevailed in the applications of these facilities for many years, several new topics have appeared recently. By combining their ability to generate highly clustered damages in a micrometric volume with immunostaining or live-cell GFP labelling, a huge potential for monitoring radiation-induced DNA damage and repair has been introduced. This type of studies has pushed end-stations towards advanced fluorescence microscopy techniques, and several microbeam lines are currently equipped with the state-of-the-art time-lapse fluorescence imaging microscopes. In addition, CPMs are nowadays also used to irradiate multicellular models in a highly controlled way. This review presents the latest developments and applications of charged-particle microbeams to radiation biology.


Assuntos
Aceleradores de Partículas/instrumentação , Radiobiologia/instrumentação , Radiobiologia/métodos , Efeito Espectador , Dano ao DNA/efeitos da radiação , Humanos , Doses de Radiação
17.
Radiat Oncol ; 10: 42, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25880907

RESUMO

Ion microbeams are important tools in radiobiological research. Still, the worldwide number of ion microbeam facilities where biological experiments can be performed is limited. Even fewer facilities combine ion microirradiation with live-cell imaging to allow microscopic observation of cellular response reactions starting very fast after irradiation and continuing for many hours. At SNAKE, the ion microbeam facility at the Munich 14 MV tandem accelerator, a large variety of biological experiments are performed on a regular basis. Here, recent developments and ongoing research projects at the ion microbeam SNAKE are presented with specific emphasis on live-cell imaging experiments. An overview of the technical details of the setup is given, including examples of suitable biological samples. By ion beam focusing to submicrometer beam spot size and single ion detection it is possible to target subcellular structures with defined numbers of ions. Focusing of high numbers of ions to single spots allows studying the influence of high local damage density on recruitment of damage response proteins.


Assuntos
Células/metabolismo , Células/efeitos da radiação , Imagem Molecular/instrumentação , Aceleradores de Partículas/instrumentação , Radiobiologia/instrumentação , Humanos , Íons
18.
J Radiat Res ; 56(3): 485-92, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25694476

RESUMO

Orthovoltage irradiators are routinely used to irradiate specimens and small animals in biological research. There are several reports on the characteristics of these units for small field irradiations. However, there is limited knowledge about use of these units for large fields, which are essential for emerging large-field irregular shape irradiations, namely total marrow irradiation used as a conditioning regimen for hematological malignancies. This work describes characterization of a self-contained Orthovoltage biological irradiator for large fields using measurements and Monte Carlo simulations that could be used to compute the dose for in vivo or in vitro studies for large-field irradiation using this or a similar unit. Percentage depth dose, profiles, scatter factors, and half-value layers were measured and analyzed. A Monte Carlo model of the unit was created and used to generate depth dose and profiles, as well as scatter factors. An ion chamber array was also used for profile measurements of flatness and symmetry. The output was determined according to AAPM Task Group 61 guidelines. The depth dose measurements compare well with published data for similar beams. The Monte Carlo-generated depth dose and profiles match our measured doses to within 2%. Scatter factor measurements indicate gradual variation of these factors with field size. Dose rate measured by placing the ion chamber atop the unit's steel plate or solid water indicate enhanced readings of 5 to 28% compared with those measured in air. The stability of output over a 5-year period is within 2% of the 5-year average.


Assuntos
Desenho Assistido por Computador , Modelos Estatísticos , Doses de Radiação , Radiobiologia/instrumentação , Irradiação Corporal Total/instrumentação , Irradiação Corporal Total/veterinária , Animais , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Radiometria , Espalhamento de Radiação
20.
J Environ Pathol Toxicol Oncol ; 32(3): 263-73, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24266413

RESUMO

Understanding the effect of alpha radiation on biological systems is an important component of radiation risk assessment and associated health consequences. However, due to the short path length of alpha radiation in the atmosphere, in vitro radiobiological experiments cannot be performed with accuracy in terms of dose and specified exposure time. The present paper describes the design and dosimetry of an automated alpha-particle irradiator named 'BARC BioAlpha', which is suitable for in vitro radiobiological studies. Compared to alpha irradiators developed in other laboratories, BARC BioAlpha has integrated computer-controlled movement of the alpha-particle source, collimator, and electronic shutter. The diaphragm blades of the electronic shutter can control the area (diameter) of irradiation without any additional shielding, which is suitable for radiobiological bystander studies. To avoid irradiation with incorrect parameters, a software interlock is provided to prevent shutter opening, unless the user-specified speed of the source and collimator are achieved. The dosimetry of the alpha irradiator using CR-39 and silicon surface barrier detectors showed that ~4 MeV energy of the alpha particle reached the cells on the irradiation dish. The alpha irradiation was also demonstrated by the evaluation of DNA double-strand breaks in human cells. In conclusion, 'BARC BioAlpha' provides a user-friendly alpha irradiation system for radiobiological experiments with a novel automation mechanism for better accuracy of dose and exposure time.


Assuntos
Partículas alfa/uso terapêutico , Neoplasias Pulmonares/radioterapia , Radiobiologia/instrumentação , Radiometria/instrumentação , Partículas alfa/efeitos adversos , Linhagem Celular Tumoral , DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Técnicas In Vitro , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Polietilenoglicóis , Silício , Software , Fatores de Tempo
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