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1.
Artigo em Inglês | MEDLINE | ID: mdl-38750904

RESUMO

PURPOSE: Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biologic effect of varying dose rates, time structure, and introducing pauses in the dose delivery. METHODS AND MATERIALS: The right hind limbs of nonanaesthetized mice were irradiated in the entrance plateau of a pencil beam scanning proton beam with 39.3 Gy. Experiment 1 was with varying field dose rates (0.7-80 Gy/s) without repainting, experiment 2 was with varying field dose rates (0.37-80 Gy/s) with repainting, and in experiment 3, the dose was split into 2, 3, 4, or 6 identical deliveries with 2-minute pauses. In total, 320 mice were included, with 6 to 25 mice per group. The endpoints were skin toxicity of different levels up to 25 days after irradiation. RESULTS: The dose rate50, which is the dose rate to induce a response in 50% of the animals, depended on the level of skin toxicity, with the higher toxicity levels displaying a FLASH effect at 0.7-2 Gy/s. Repainting resulted in higher toxicity for the same field dose rate. Splitting the dose into 2 deliveries reduced the FLASH effect, and for 3 or more deliveries, the FLASH effect was almost abolished for lower grades of toxicity. CONCLUSIONS: The dose rate that induced a FLASH effect varied for different skin toxicity levels, which are characterized by a differing degree of sensitivity to radiation dosage. Conclusions on a threshold for the dose rate needed to obtain a FLASH effect can therefore be influenced by the dose sensitivity of the used endpoint. Splitting the total dose into more deliveries compromised the FLASH effect. This can have an impact for fractionation as well as for regions where 2 or more FLASH fields overlap within the same treatment session.

2.
Materials (Basel) ; 17(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38541603

RESUMO

This paper presents a research program aimed towards developing a method of producing lightweight, porous geopolymer composites for the construction industry based on industrial wastes. A direct method involving the addition of chemicals is currently most commonly used to produce the porous mineral structure of a geopolymer matrix. This relies on a reaction in a highly alkaline environment of the geopolymer to produce a gas (usually hydrogen or oxygen) that forms vesicles and creates a network of pores. This paper demonstrates the feasibility of producing a slag-based geopolymer paste foamed with aluminum powder, taking into account different parameters of fresh paste production: the mixing duration, its speed and the timing of foaming agent addition. The foaming process of the fresh paste in terms of the volumetric changes and temperature development of the fresh paste during the curing of the material are observed. After hardening, the physical properties (density and porosity) as well as the mechanical parameters (compressive strength and work of damage) are determined for the nine manufactured foamed pastes. Image analysis software was used to assess the porosity distribution of the material across the cross-section of the samples. The results enabled the design of the mixing procedure to be adopted during the manufacture of such composites.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38462015

RESUMO

PURPOSE: The aim of this work was to investigate the ability of a biological oxygen enhancement ratio-weighted dose, DOER, to describe acute skin toxicity variations observed in mice after proton pencil beam scanning irradiations with changing doses and beam time structures. METHODS AND MATERIALS: In five independent experiments, the right hind leg of a total of 621 CDF1 mice was irradiated previously in the entrance plateau of a pencil beam scanning proton beam. The incidence of acute skin toxicity (of level 1.5-2.0-2.5-3.0-3.5) was scored for 47 different mouse groups that mapped toxicity as function of dose for conventional and FLASH dose rate, toxicity as function of field dose rate with and without repainting, and toxicity when splitting the treatment into 1 to 6 identical deliveries separated by 2 minutes. DOER was calculated for all mouse groups using a simple oxygen kinetics model to describe oxygen depletion. The three independent model parameters (oxygen-depletion rate, oxygen-recovery rate, oxygen level without irradiation) were fitted to the experimental data. The ability of DOER to describe the toxicity variations across all experiments was investigated by comparing DOER-response curves across the five independent experiments. RESULTS: After conversion from the independent variable tested in each experiment to DOER, all five experiments had similar MDDOER50 (DOER giving 50% toxicity incidence) with standard deviations of 0.45 - 1.6 Gy for the five toxicity levels. DOER could thus describe the observed toxicity variations across all experiments. CONCLUSIONS: DOER described the varying FLASH-sparing effect observed for a wide range of conditions. Calculation of DOER for other irradiation conditions can quantitatively estimate the FLASH-sparing effect for arbitrary irradiations for the investigated murine model. With appropriate fitting parameters DOER also may be able to describe FLASH effect variations with dose and dose rate for other assays and endpoints.

4.
Acta Oncol ; 63: 23-27, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349282

RESUMO

BACKGROUND: Radiobiological experimental setups are challenged by precise sample positioning along depth dose profile, scattering conditions, and practical difficulties that must be addressed in individual designs. The aim of this study was to produce cell survival curves with several irradiation modalities, by using a setup designed at the Danish Centre for Particle Therapy (DCPT) for in vitro proton irradiations using a horizontal beam line and thereby evaluating the setups use for in vitro irradiations experiments. MATERIALS AND METHODS: The setup is a water phantom suitable for in vitro research with multiple irradiation modalities, in particular the pencil scanning proton beam available from a horizontal experimental beamline. The phantom included a water tank of 39.0 × 17.0 × 20.5 cm. Cell survival-curves were produced using the cell line V79 Chinese hamster lung fibroblast cells (V79s) in biological triplicates of clonogenic assays. Cell survival curves were produced with both a 18 MeV electron beam, 6 MV photon beam, and a Spread-Out Bragg Peak (SOBP) proton beam formed by pristine energies of 85-111 MeV where three positions were examined. RESULTS: Survival curves with uncertainty areas were made for all modalities. Dosimetric uncertainty amounted to, respectively, 4%, 3% and 3% for proton, electron, and high energy photon irradiations. Cell survival fraction uncertainty was depicted as the standard deviation between replications of the experiment. CONCLUSION: Cell survival curves could be produced with acceptable uncertainties using this novel water phantom and cellular laboratory workflow. The setup is useful for future in vitro irradiation experiments.


Assuntos
Fótons , Prótons , Animais , Cricetinae , Humanos , Sobrevivência Celular , Água , Dinamarca
5.
Int J Mol Sci ; 24(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38069306

RESUMO

Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy from either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography-mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/radioterapia , Neoplasias Bucais/patologia , Prótons , Raios X , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteínas/análise , Neoplasias de Cabeça e Pescoço/patologia , Vesículas Extracelulares/patologia
6.
Materials (Basel) ; 16(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38138761

RESUMO

This paper focuses on the development of thin-walled panels with specific properties for applications such as water-tight structures. The authors propose the use of textile-reinforced concrete (TRC) as a composite material and highlight its advantages, which include high tensile strength, improved crack resistance, and design flexibility. The study presents a novel approach which combines TRC with reactive powder concrete (RPC) as a matrix and a lightweight aggregate. RPC, known for its brittle behaviour, is reinforced with glass fibres and a textile fabric to increase its flexural strength. The research includes a comprehensive analysis of the physical and mechanical properties of both the unreinforced RPC matrix and the TRC composite. In particular, the lightweight aggregate RPC matrix has a porosity of 41%, and its mechanical properties, such as flexural and compressive strength, are discussed. The TRC composites, produced in thicknesses ranging from 1 mm to 4 mm, are subjected to flexural tests to evaluate their behaviour under load. The thicker elements show typical damage phases, while the thinner elements show greater flexibility and elasticity. SEM observations confirm good adhesion between the glass fibres and the RPC matrix. Water permeability tests show that the TRC composite, despite its highly porous structure, achieves a water permeability two orders of magnitude higher than that of a reference material, highlighting the roles of both the porous aggregate and the matrix hydration. The paper concludes with a proof of concept-a canoe called the PKanoe, which is constructed from the developed TRC composite. The design of the canoe is supported by numerical analysis to ensure its optimal shape and structural integrity under load. The research contributes to the exploration of innovative materials for sustainable civil engineering applications and addresses both structural and environmental considerations.

8.
Acta Oncol ; 62(11): 1574-1580, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37703217

RESUMO

BACKGROUND: The purpose of this study was to investigate acute normal tissue responses in the head and neck region following proton- or X-irradiation of a murine model. MATERIALS AND METHODS: Female C57BL/6J mice were irradiated with protons (25 or 60 MeV) or X-rays (100 kV). The radiation field covered the oral cavity and the major salivary glands. For protons, two different treatment plans were used, either with the Bragg Peak in the middle of the mouse (BP) or outside the mouse (transmission mode; TM). Delivered physical doses were 41, 45, and 65 Gy given in 6, 7, and 10 fractions for BP, TM, and X-rays, respectively. Alanine dosimetry was used to assess delivered doses. Oral mucositis and dermatitis were scored using CTC v.2.0-based tables. Saliva was collected at baseline, right after end of irradiation, and at day 35. RESULTS: The measured dose distribution for protons (TM) and X-rays was very similar. Oral mucositis appeared earlier, had a higher score and was found in a higher percentage of mice after proton irradiation compared to X-irradiation. Dermatitis, on the other hand, had a similar appearance after protons and X-rays. Compared to controls, saliva production was lower right after termination of proton- and X-irradiation. The BP group demonstrated saliva recovery compared to the TM and X-ray group at day 35. CONCLUSION: With lower delivered doses, proton irradiation resulted in similar skin reactions and increased oral mucositis compared to X-irradiation. This indicates that the relative biological effectiveness of protons for acute tissue responses in the mouse head and neck is greater than the clinical standard of 1.1. Thus, there is a need for further investigations of the biological effect of protons in normal tissues.


Assuntos
Dermatite , Estomatite , Feminino , Camundongos , Animais , Prótons , Raios X , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
9.
Acta Oncol ; 62(11): 1566-1573, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37603112

RESUMO

BACKGROUND: The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. METHODS: The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. RESULTS: The dose-response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose-response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. CONCLUSIONS: We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.


Assuntos
Terapia com Prótons , Prótons , Animais , Camundongos , Reprodutibilidade dos Testes , Terapia com Prótons/métodos , Radiometria/métodos , Modelos Teóricos , Método de Monte Carlo
10.
Sensors (Basel) ; 23(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37571670

RESUMO

The response of Timepix3 detectors with 300 µm and 500 µm thick HR GaAs:Cr sensors was studied with particle beams at the Danish Centre for Particle Therapy in Aarhus, Denmark. Therefore, the detectors were irradiated at different angles with protons of 240 MeV. The precise per-pixel time and energy measurements were exploited in order to determine the charge carrier transport properties. Using the tracks left by the penetrating charged particles hitting the sensor at the grazing angle, we were able to determine the charge collection efficiency, the charge carrier drift times across the sensor thickness, the dependency of the electron, and for the first time, the hole drift velocity on the electric field. Moreover, extracting the dependence of the charge cloud size on the interaction depth for different bias voltages, it was possible to determine the dependence of the diffusion coefficient on the applied bias voltage. A good agreement was found with the previously reported values for n-type GaAs. The measurements were conducted for different detector assemblies to estimate the systematic differences between them, and to generalize the results. The experimental findings were implemented into the Allpix Squared simulation framework and validated by a comparison of the measurement and simulation for the 241Am γ-ray source.

11.
Acta Oncol ; 62(11): 1581-1586, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37498559

RESUMO

BACKGROUND: The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons. MATERIALS AND METHODS: Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm3. Radiation was delivered with an 83-107MeV pencil scanning proton beam in the centre of a 3 cm spread out Bragg peak. Following irradiation (day 0), mice were injected intraperitoneal with anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints were tumour growth time (TGT3; time to reach 3 times treatment volume) or local tumour control (percent of mice showing tumour control at 90 days). A Student's T-test (tumour growth) or Chi-squared test (tumour control) were used for statistical analysis; significance levels of p < 0.05. RESULTS: Untreated tumours had a mean (± 1 S.E.) TGT3 of 4.6 days (± 0.4). None of the checkpoint inhibitors changed this TGT3. A linear increase in TGT3 was seen with increasing radiation doses (5-20 Gy), reaching 17.2 days (± 0.7) with 20 Gy. Anti-CTLA-4 had no effect on radiation doses up to 15 Gy, but significantly enhanced 20 Gy; the TGT3 being 23.0 days (± 1.3). Higher radiation doses (35-60 Gy) were investigated using a tumour control assay. Logit analysis of the dose response curve, resulted in a TCD50 value (radiation dose causing 50% tumour control; with 95% confidence intervals) of 48 Gy (44-53) for radiation only. This significantly decreased to 43 Gy (38-49) when mice were treated with anti-CTLA-4. Neither anti-PD-1 nor anti-PD-L1 significantly affected tumour control. CONCLUSION: Checkpoint inhibitors enhanced the response of this C3H mammary carcinoma to proton irradiation. However, this enhancement depended on the checkpoint inhibitor and radiation dose.


Assuntos
Carcinoma , Prótons , Camundongos , Masculino , Animais , Camundongos Endogâmicos C3H , Imunoterapia
12.
Med Phys ; 50(4): 2450-2462, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36508162

RESUMO

BACKGROUND: The spatial and temporal dose rate distribution of pencil beam scanning (PBS) proton therapy is important in ultra-high dose rate (UHDR) or FLASH irradiations. Validation of the temporal structure of the dose rate is crucial for quality assurance and may be performed using detectors with high temporal resolution and large dynamic range. PURPOSE: To provide time-resolved in vivo dose rate measurements using a scintillator-based detector during proton PBS pre-clinical mouse experiments with dose rates ranging from conventional to UHDR. METHODS: All irradiations were performed at the entrance plateau of a 250 MeV PBS proton beam. A detector system with four fiber-coupled ZnSe:O inorganic scintillators and 20 µs temporal resolution was used for dose rate measurements. The system was first characterized in terms of precision and stem signal. The detector precision was determined through repeated irradiations with the same field. The stem signal contribution was quantified by irradiating two of the detector probes alongside a bare fiber (fiber without a coupled scintillator). Next, the detector system was calibrated against an ionization chamber (IC) with all four detector probes and the IC placed in a water bath at 2 cm depth. A scan pattern covering 9.6 × 9.6 cm was used. Multiple irradiations with different requested nozzle currents provided instantaneous dose rates at the detector positions in the range of 7-1270 Gy/s. The correspondence of the detector signal (in Volts) to the instantaneous dose rate (in Gy/s) was found. The instantaneous dose rate was calculated from the beam current and the spot-to-detector distance assuming a Gaussian beam profile at distances up to 8 mm from the spot. Afterwards, the calibrated system was used in vivo, in mouse experiments, where mouse legs were irradiated with a constant dose and varying field dose rates of 0.7-87.5 Gy/s. The instantaneous dose rate was measured for each delivered spot and the delivered dose was determined as the integrated instantaneous dose rate. The spot dose profile and PBS dose rate map were calculated. The dose contamination to neighbouring mice were measured together with the upper limit of the dose to the mouse body. RESULTS: The detectors showed high precision with ≤0.4% fluctuations in the measured dose. The stem signal exceeded 10% for spots <5 mm from the optical fiber and >18 mm from the scintillator. It contributed up to 0.2% to the total dose, which was considered negligible. All four detectors showed a non-linear relation between signal and instantaneous dose rate, which was modelled with a polynomial response function. In the mouse experiments, the measured scintillator dose showed 1.8% fluctuations, independent of the field dose rate. The in vivo measured spot dose profile had tails that deviated from a Gaussian profile with measurable dose contributions from spots up to 85 mm from the detector. Neighbour mouse irradiation contributed ∼1% of the total mouse dose. The upper limit of the mouse body dose was 6% of the mouse leg dose. CONCLUSIONS: A fiber-coupled inorganic scintillator-based detector system can provide high precision in vivo measurements of the instantaneous dose rate if correction for the non-linear dose rate dependency is applied.


Assuntos
Terapia com Prótons , Prótons , Radiometria , Dosagem Radioterapêutica
13.
Radiother Oncol ; 175: 178-184, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35595175

RESUMO

PURPOSE: Preclinical studies indicate a normal tissue sparing effect when ultra-high dose rate (FLASH) radiation is used, while tumor response is maintained. This differential response has promising perspectives for improved clinical outcome. This study investigates tumor control and normal tissue toxicity of pencil beam scanning (PBS) proton FLASH in a mouse model. METHODS AND MATERIALS: Tumor bearing hind limbs of non-anaesthetized CDF1 mice were irradiated in a single fraction with a PBS proton beam using either conventional (CONV) dose rate (0.33-0.63 Gy/s field dose rate, 244 MeV) or FLASH (71-89 Gy/s field dose rate, 250 MeV). 162 mice with a C3H mouse mammary carcinoma subcutaneously implanted in the foot were irradiated with physical doses of 40-60 Gy (8-14 mice per dose point). The endpoints were tumor control (TC) assessed as no recurrent tumor at 90 days after treatment, the level of acute moist desquamation (MD) to the skin of the foot within 25 days post irradiation, and radiation induced fibrosis (RIF) within 24 weeks post irradiation. RESULTS: TCD50 (dose for 50% tumor control) was similar for CONV and FLASH with values (and 95% confidence intervals) of 49.1 (47.0-51.4) Gy for CONV and 51.3 (48.6-54.2) Gy for FLASH. RIF analysis was restricted to mice with tumor control. Both endpoints showed distinct normal tissue sparing effect of proton FLASH with MDD50 (dose for 50% of mice displaying moist desquamation) of <40.1 Gy for CONV and 52.3 (50.0-54.6) Gy for FLASH, (dose modifying factor at least 1.3) and FD50 (dose for 50% of mice displaying fibrosis) of 48.6 (43.2-50.8) Gy for CONV and 55.6 (52.5-60.1) Gy for FLASH (dose modifying factor of 1.14). CONCLUSIONS: FLASH had the same tumor control as CONV, but reduced normal tissue damage assessed as acute skin damage and radiation induced fibrosis.


Assuntos
Terapia com Prótons , Prótons , Camundongos , Animais , Camundongos Endogâmicos C3H , Recidiva Local de Neoplasia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Pele/efeitos da radiação , Dosagem Radioterapêutica
15.
Med Phys ; 49(3): 1932-1943, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35076947

RESUMO

PURPOSE: Key factors in FLASH treatments are the ultra-high dose rate (UHDR) and the time structure of the beam delivery. Measurement of the time structure in pencil beam scanning (PBS) proton FLASH treatments is challenging for many types of detectors since high temporal resolution is needed. In this study, a fast scintillator detector system was developed and used to measure the individual spot durations as well as the time when the beam moves between two positions (transition duration) during PBS proton FLASH and UHDR treatments. The spot durations were compared with machine log-file recordings. METHODS: A detector system based on inorganic scintillating crystals was developed. The system consisted of four detector probes made of a sub-millimeter ZnSe:O crystal that was coupled via an optical fiber to an optical reader with 50 kHz sampling rate. The detector system was used in two experiments, both performed with a PBS proton beam with 250 MeV beam energy and 215 nA requested nozzle beam current. The sampling rate enabled multiple measurements during each spot delivery and during the beam transition between spots. First, the detector was tested in a phantom experiment, where a total of 305 scan sequences were delivered to the four detectors. The number of spots delivered without beam interruption in a single scan sequence ranged from one to 35. The spot duration and transition duration were measured for each individual spot. Secondly, the detector system was used in vivo in preclinical experiments with FLASH irradiation of mouse legs placed in the entrance plateau of the beam. A single detector was placed 1 cm downstream of the irradiated mouse leg. The mouse dose ranged from 30.5 to 44.2 Gy and the field consisted of 35 spots. The spot durations as well as the mean dose rate (field dose divided by the measured field duration) for each mouse were determined using the detector and then compared with the corresponding log files. RESULTS: The phantom experiment showed that the logged total duration of an uninterrupted spot sequence was consistently shorter than the measured duration with a difference of -0.252 ms (95% confidence interval: [-0.255, -0.249 ms]). This corresponded to 0.05%-0.07% of the spot sequence duration in the mice experiments. For individual spots, the mean ± 1SD difference between logged and measured spot duration was -0.39 ± 0.05 ms for the first spot in a sequence, 0.13 ± 0.04 ms for the last spot in a sequence, and -0.0017 ± 0.09 ms for the intermediate spots in a sequence. The measured spot transition durations were 0.20 ± 0.04 ms (5.1 mm horizontal steps) and 0.50 ± 0.04 ms (5.0 mm vertical steps). For the mouse experiments, the mean dose rate calculated from the measured field duration was 84.1-92.5 Gy/s. It agreed with log files with a root mean square difference of 0.02 Gy/s. CONCLUSIONS: Fiber-coupled scintillator detectors were designed with sufficient temporal resolution to measure the spot and transition duration during PBS proton UHDR deliveries. Their small volume makes them feasible for in vivo use in preclinical FLASH studies. The logged spot durations were in excellent agreement with measurements but showed small systematic errors in the logged duration for the first and last spot in a sequence.


Assuntos
Terapia com Prótons , Prótons , Animais , Camundongos , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
16.
Radiother Oncol ; 167: 109-115, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34953933

RESUMO

BACKGROUND AND PURPOSE: Preclinical studies indicate a normal tissue sparing effect using ultra-high dose rate (FLASH) radiation with comparable tumor response. Most data so far are based on electron beams with limited utility for human treatments. This study validates the effect of proton FLASH delivered with pencil beam scanning (PBS) in a mouse leg model of acute skin damage and quantifies the normal tissue sparing factor, the FLASH factor, through full dose response curves. MATERIALS AND METHODS: The right hind limb of CDF1 mice was irradiated with a single fraction of proton PBS in the entrance plateau of either a 244 MeV conventional dose rate field or a 250 MeV FLASH field. In total, 301 mice were irradiated in four separate experiments, with 7-21 mice per dose point. The endpoints were the level of acute moist desquamation to the skin of the foot within 25 days post irradiation. RESULTS: The field duration and field dose rate were 61-107 s and 0.35-0.40 Gy/s for conventional dose rate and 0.35-0.73 s and 65-92 Gy/s for FLASH. Full dose response curves for five levels of acute skin damage for both conventional and FLASH dose rate revealed a distinct normal tissue sparing effect with FLASH: across all scoring levels, a 44-58% higher dose was required to give the same biological response with FLASH as compared to the conventional dose rate. CONCLUSIONS: The normal tissue sparing effect of PBS proton FLASH was validated. The FLASH factor was quantified through full dose response curves.


Assuntos
Terapia com Prótons , Prótons , Animais , Humanos , Camundongos , Dosagem Radioterapêutica , Tromboplastina
17.
Materials (Basel) ; 14(21)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34772108

RESUMO

Due to the need to reduce the CO2 emissions of mineral binders, researchers are considering the use of alkali-activated materials (AAMs) as an alternative to cementitious binders. The properties of AAMs can be more advantageous than those presented by cementitious binders, and thus they can replace Portland cement binders in some applications. Mechanical tests of AAMs are being conducted on an ongoing basis; however, durability issues related to reinforcing steel in conditions in which steel members interact with chloride ions remain unsolved. In this paper, the precursors for AAM preparations are blends of fly ash (FA) and ground granulated blast-furnace slag (GGBFS) in four slag proportions: 0%, 10%, 30% and 50% expressed as a percent of FA mass. Four alkali-activated mortars were prepared, denominated as AAM 0, AAM 10, AAM 30 and AAM 50, respectively. Their basic physical and mechanical characteristics were investigated, as were their gas transport properties. The nitrogen Cembureau method was applied to determine the permeability of the mortar. The transport properties of the chloride ions were determined using the modified NT BUILD 492 migration test. The comparison of results obtained demonstrated a positive effect of GGBFS addition in terms of an increase in bulk density, permeability, porosity and, at the same time, a reduction in chloride ion penetration. The water absorption tests also provided insight into the open pore structures of mortars. The measurements revealed a strong dependence between fluid transport through the mortars and the water absorption and initial water content of materials.

18.
Materials (Basel) ; 15(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35009357

RESUMO

Mineral geopolymer binders can be an attractive and more sustainable alternative to traditional Portland cement materials for special applications. In geopolymer technology the precursor is a source of silicon and aluminium oxides, the second component is an alkaline solution. In the synthesis of geopolymer binders the most commonly used alkaline solution is a mixture of sodium or potassium water glass with sodium or potassium hydroxide or silicate solution with a low molar ratio, which is more convenient and much safer in use. In this paper, we present the influence of sodium or potassium silicate solution on the physical and mechanical properties of fly ash and ground granulated blast furnace slag-based geopolymer mortars. Mercury intrusion porosimetry and microstructural observation allowed for comparing the structure of materials with a different type of alkaline solution. The evolution of compressive and flexural tensile strength with time determined for composites using 10%, 30% and 50% slag contents (referring to fly ash mass) was analysed. The tests were performed after 3, 7, 14 and 28 days. It was observed that, as the amount of slag used increases in the precursor, the strength of the material grows. Mortars with the sodium alkaline solution were characterised by a higher strength at a young age. However, the values of strength 28 days were higher for geopolymers with potassium alkaline solution reaching 75 MPa in compression. Geopolymer mortar microstructure observation indicates a high matrix heterogeneity with numerous microcracks. Matrix defects may be caused by the rapid kinetics of the material binding reaction or shrinkage associated with the drying of the material.

19.
Materials (Basel) ; 13(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987886

RESUMO

The inorganic structure formed at the stage of setting of the geopolymer binder ensures high durability of the material under high-temperature conditions. However, changes in the microstructure of the material are observed. The purpose of the study was to analyze changes in the structure of geopolymer mortar after exposure to high temperatures T = 200, 400, 600, 800, and 1000 °C. Mortars with a binder based solely on fly ash (FA) and mixed in the 1:1 ratio with a binder containing fly ash and ground granulated blast-furnace slag (GGBFS) were tested. The descriptions of their microstructures were prepared based on digital microscope observations, scanning electron microscope (SEM) observations, EDS (energy dispersive spectroscopy) analysis, and mercury intrusion porosimetry (MIP) porosity test results. Changes in the material due to high temperature were observed. The differences in the microstructure of the samples are also visible in the materials that were not exposed to temperature, which was influenced by the composition of the materials. Porosity increases with increasing annealing temperature. The distribution of individual pores also changes. In both materials, the proportion of pores larger than 1000 nm increases with the temperature increase. Moreover, the number of cracks and their width also increases, reaching 20 µm in the case of GGBFS. Furthermore, the color of geopolymers has changed. The obtained results extend the current state of knowledge in the field of changes in the microstructure of geopolymers subjected to high temperature.

20.
Appl Radiat Isot ; 155: 108898, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31577965

RESUMO

Following the advancement of the Positron Emission Tomography (PET), a novel technique emerged which takes advantage of the gamma quanta emitted, in some cases, after the ß+ decay. While 44gSc is commonly agreed the best choice to validate this new modality, other radioisotopes must also be considered in the future. We present them in this paper, along with their possible applications, properties and the optimal production routes with the use of the accelerators.

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