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1.
Environ Sci Pollut Res Int ; 31(21): 31015-31027, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38619766

RESUMO

The 5G sub-6 GHz radio frequency (RF) electromagnetic fields (EMF) are the most widely used in China's communications. The public has expressed concerns about possible brain health effects of the higher frequency bands in 5G compared to 2G, 3G, and 4G bands. It is imperative to empirically investigate the potential health hazards of these novel frequency bands in 5G communication technology. This study evaluates the assessment of brain tissue dose coupling from sub-6 GHz band EMF emitted by base stations in China. Based on the 3D virtual human body model, the simulation environment was established. Dose including specific absorption rate (SAR) and internal electric field (IEF) between 2G, 3G, and 4G bands and 5G sub-6 GHz was investigated using normalized exposure values and exposure limits. The results indicate that the sub-6 GHz high-frequency band of 5G has the lowest dose value. It can be concluded that high-frequency electromagnetic radiation in 5G sub-6 GHz reduces the dose and health threats to the brain. This provides strong support for the promotion of 5G commutation in China and other regions.


Assuntos
Encéfalo , Campos Eletromagnéticos , Ondas de Rádio , China , Humanos , Encéfalo/efeitos da radiação , Radiação Eletromagnética
2.
Int J Mol Sci ; 22(24)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34947991

RESUMO

DNA-double strand break (DSB), detected by immunostaining of key proteins orchestrating repair, like γH2AX and 53BP1, is well established as a surrogate for tissue radiosensitivity. We hypothesized that the generation of normal brain 3D organoids ("mini-brains") from human induced pluripotent stem cells (hiPSC) combined with detection of DNA damage repair (DDR) may hold the promise towards developing personalized models for the determination of normal tissue radiosensitivity. In this study, cerebral organoids, an in vitro model that stands in its complexity between 2D cellular system and an organ, have been used. To quantify radiation-induced response, immunofluorescent staining with γH2AX and 53BP1 were applied at early (30 min, initial damage), and late time points (18 and 72 h, residual damage), following clinical standard 2 Gy irradiation. Based on our findings, assessment of DDR kinetics as a surrogate for radiosensitivity in hiPSC derived cerebral organoids is feasible. Further development of mini-brains recapitulating mature adult neuronal tissue and implementation of additional signaling and toxicity surrogates may pave the way towards development of next-generation personalized assessment of radiosensitivity in healthy neuronal tissue.


Assuntos
Encéfalo/citologia , Dano ao DNA , Organoides/citologia , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Células Cultivadas , Histonas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos da radiação , Técnicas de Cultura de Órgãos , Organoides/metabolismo , Organoides/efeitos da radiação , Doses de Radiação , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
3.
PLoS One ; 16(9): e0257638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534258

RESUMO

Some concepts in nuclear radiation physics are abstract and intellectually demanding. In the present paper, an "MCHP platform" (MCHP was an acronym for Monte Carlo simulations + Human Phantoms) was proposed to provide assistance to the students through visualization. The platform involved Monte Carlo simulations of interactions between ionizing radiations and the Oak Ridge National Laboratory (ORNL) adult male human phantom. As an example to demonstrate the benefits of the proposed MCHP platform, the present paper investigated the variation of the absorbed photon dose per photon from a 137Cs source in three selected organs, namely, brain, spine and thyroid of an adult male for concrete and lead shields with varying thicknesses. The results were interesting but not readily comprehensible without direct visualization. Graphical visualization snapshots as well as video clips of real time interactions between the photons and the human phantom were presented for the involved cases, and the results were explained with the help of such snapshots and video clips. It is envisaged that, if the platform is found useful and effective by the readers, the readers can also propose examples to be gradually added onto this platform in future, with the ultimate goal of enhancing students' understanding and learning the concepts in an undergraduate nuclear radiation physics course or a related course.


Assuntos
Método de Monte Carlo , Física Nuclear/educação , Proteção Radiológica/métodos , Encéfalo/efeitos da radiação , Radioisótopos de Césio/química , Corpo Humano , Humanos , Fótons , Proteção Radiológica/instrumentação , Radiação Ionizante , Radiometria , Estudantes
4.
J Radiat Res ; 62(5): 793-803, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34062561

RESUMO

The objective of the study was to describe cellular and molecular markers of radioprotection by anisomycin, focusing on the changes in rat brain tissue. Two-month-old Wistar rats were exposed to a 60Co radiation source at a dose of 6 Gy, with or without radioprotection with anisomycin (150 mg/kg) administered subcutaneously 30 min before or 3 or 6 h after irradiation. Survivors were analyzed 30 days after treatment. Astroglial and microglial responses were investigated based on the expression of glial markers assessed with immunohistochemistry, and quantitative changes in brain biomolecules were investigated by Raman microspectroscopy. In addition, blood plasma levels of pro-inflammatory (interleukin 6 and tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were assessed. We found that application of anisomycin either before or after irradiation significantly decreased the expression of the microglial marker Iba-1. We also found an increased intensity of Raman spectral bands related to nucleic acids, as well as an increased level of cytokines when anisomycin was applied after irradiation. This suggests that the radioprotective effects of anisomycin are by decreasing Iba-1 expression and stabilizing genetic material by increasing the level of nucleic acids.


Assuntos
Anisomicina/uso terapêutico , Encéfalo/efeitos da radiação , Irradiação Craniana/efeitos adversos , Raios gama/efeitos adversos , Lesões Experimentais por Radiação/metabolismo , Protetores contra Radiação/uso terapêutico , Animais , Anisomicina/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/efeitos da radiação , Encéfalo/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Radioisótopos de Cobalto , Citocinas/sangue , Proteínas dos Microfilamentos/biossíntese , Proteínas dos Microfilamentos/genética , Microglia/efeitos dos fármacos , Microglia/efeitos da radiação , Ácidos Nucleicos/metabolismo , Pré-Medicação , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Ratos , Ratos Wistar
5.
Radiat Res ; 195(6): 568-583, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33826744

RESUMO

In utero exposure to ionizing radiation can lead to cerebral alterations during adulthood. Using anatomical magnetic resonance imaging (MRI), it is possible to assess radiation-induced structural brain damage noninvasively. However, little is currently known about microstructure alterations in brain tissue. Therefore, the goal of this study was to establish, based on an original and robust pipeline of MRI image analysis, whether the long-term effects of in utero radiation exposure on brain tissue microstructure could be detected noninvasively. Pregnant C57BL/6N mice received a single dose of 1 Gy on gestation day 14.5, which led to behavioral impairments in adults. At 3 months old, in vivo MRI data were acquired from in utero irradiated and nonirradiated male mice. An MRI protocol was designed to assess the effects of radiation on the parameters of brain volume, non-Gaussian diffusion (ADC0, kurtosis and signature index) and anisotropic diffusion (fractional anisotropy and mean, axial, radial diffusivities and anisotropic signature index) in 10 key cerebral structures defined using an in-house atlas of the mouse brain. Based on the relative amplitude of these anatomical and microstructural changes, maps of the radiosensitivity of the brain to in utero irradiation were created. We observed microcephaly in irradiated mice with noticeably larger volume changes in the cortex and the corpus callosum. We also observed significantly lower ADC0, anisotropy fraction (sFA), radial diffusivity (sRD), as well as signature index (S-index and SI3) values, which are original markers sensitive to tissue microstructure alterations. All these changes together are in favor of a decreased cellular "imprint" and in some regions a reduced density in myelinated axons. A reduction in the number and complexity of myelinated axons was further revealed by myelin basic protein immunostaining. Combining anatomical and diffusion MRI is a promising approach to noninvasively investigate the radiosensitivity of local brain areas in adult mice after in utero irradiation in terms of microstructure.


Assuntos
Encéfalo/efeitos da radiação , Imagem de Difusão por Ressonância Magnética , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/patologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Axônios/patologia , Axônios/efeitos da radiação , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Masculino , Camundongos , Bainha de Mielina/metabolismo , Tamanho do Órgão/efeitos da radiação , Gravidez
6.
Int J Radiat Oncol Biol Phys ; 110(4): 984-992, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600889

RESUMO

PURPOSE: Uncertainties in relative biological effectiveness (RBE) constitute a major pitfall of the use of protons in clinics. An RBE value of 1.1, which is based on cell culture and animal models, is currently used in clinical proton planning. The purpose of this study was to determine RBE for temporal lobe radiographic changes using long-term follow-up data from patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Five hundred sixty-six patients with newly diagnosed nasopharyngeal carcinoma received double-scattering proton therapy or intensity modulated radiation therapy at our institutions. The 2 treatment cohorts were well matched. Proton dose distributions were simulated using Monte Carlo and compared with those obtained from the proton clinical treatment planning system. Late treatment effect was defined as development of enhancement of temporal lobe on T1-weighted magnetic resonance imaging, with or without accompanying clinical symptoms. The tolerance dose was calculated with receiving operator characteristic analysis and the Youden index. Tolerance curves, expressed as a cumulative dose-volume histogram, were generated using the cutoff points. RESULTS: With a median follow-up period >5 years for both cohorts, 10% of proton patients and 4% of patients undergoing intensity modulated radiation therapy developed temporal lobe enhancement in unilateral temporal lobe. There was no significant difference in dose distributions between the Monte Carlo method and treatment planning system. The tolerance dose-volume levels were V10 (26.1%), V20 (21.9%), V30 (14.0%), V40 (7.7%), V50 (4.8%), and V60 (3.3%) for proton therapy (P < .03). Comparison of the two tolerance curves revealed that tolerance doses of proton treatments were lower than that of photon treatments at all dose levels. The dose tolerance at D1% was 58.56 Gy for protons and 69.07 Gy for photons. The RBE for temporal lobe enhancement from proton treatments were calculated to be 1.18. CONCLUSIONS: Using long-term clinical outcome of patients with nasopharyngeal carcinoma, our data suggest that the RBE for temporal lobe enhancement is 1.18 at D1%. A prospective study in a large cohort would be necessary to confirm these findings.


Assuntos
Encéfalo/efeitos da radiação , Carcinoma Nasofaríngeo/radioterapia , Terapia com Prótons , Eficiência Biológica Relativa , Adulto , Feminino , Humanos , Masculino , Método de Monte Carlo , Estudos Prospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Resultado do Tratamento
7.
Lasers Med Sci ; 36(4): 803-810, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32638241

RESUMO

Studying light penetration in biological tissues became a very important concern in various medical applications. It is an essential factor required to resolve the optical dose in many diagnostic and therapeutic procedures. The absorption and scattering properties of the inspected tissue control how deep the light will travel inside the tissue. However, these optical properties are highly dependent on the wavelength of the light source. In this work, the light transmission through different regions of the rat's head was investigated and the minimum laser power required to reach different parts of the head is also determined using 808-nm semiconductor laser diode. The power variation in different regions of the head is estimated using Monte Carlo simulation. Absorption and scattering coefficients of the head layers were calculated using integrating sphere measurements and Kubelka-Munk model. The absorption coefficient of the skin was 0.19 ± 0.071 mm-1, 0.024 ± 0.11 mm-1 for skull, and 0.35 ± 0.13 mm-1 for the brain, while the scattering coefficients were 7.35 ± 1.09, 2.71 ± 0.37, and 13.04 ± 0.36 mm-1 for skin, skull, and brain, respectively. The obtained results provide a relationship between laser incident power and the depth in the rat's head showing a higher optical transmission at the frontal part of the head than the middle or back regions due to the variations in the skull thickness. Therefore, the study revealed that the transmitted power of 808 nm laser at different incident locations on the head is nonlinear and variable due to different skull's thickness.


Assuntos
Cabeça/efeitos da radiação , Lasers Semicondutores , Método de Monte Carlo , Fenômenos Ópticos , Animais , Encéfalo/efeitos da radiação , Simulação por Computador , Ratos , Espalhamento de Radiação , Crânio/efeitos da radiação
8.
Radiat Res ; 195(3): 230-234, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347596

RESUMO

MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered safe, previous literature suggests that GBCAs are capable of contrast-induced acute kidney injury (AKI). It is unclear if the risk for AKI is enhanced when GBCAs are administered concurrently with ionizing radiotherapy. During irradiation, gadolinium may be liberated from its chelator which may induce AKI. The goal of this work was to determine if radiation combined with GBCAs increased the incidence of AKI. Using a preclinical MRI-guided irradiation system, where MRI acquisitions and radiation delivery are performed in rapid succession, tumor-bearing mice with normal kidney function were injected with GBCA and treated with 2, 8 or 18 Gy irradiation. Renal function was assessed on days three and seven postirradiation to assess for AKI. No clinically relevant changes in blood urea nitrogen and creatinine were observed in any combination of GBCA and radiation dose. From these data, we conclude that GBCA in combination with radiation does not increase the risk for AKI in mice. Additional investigation of multiple doses of GBCA administered concurrently with irradiation is warranted to evaluate the risk of chronic kidney injury.


Assuntos
Injúria Renal Aguda/diagnóstico por imagem , Meios de Contraste/farmacologia , Compostos Organometálicos/farmacologia , Radiação Ionizante , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Meios de Contraste/efeitos adversos , Modelos Animais de Doenças , Gadolínio/efeitos adversos , Gadolínio/farmacologia , Humanos , Rim/diagnóstico por imagem , Rim/efeitos dos fármacos , Rim/patologia , Rim/efeitos da radiação , Imageamento por Ressonância Magnética , Camundongos , Compostos Organometálicos/efeitos adversos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos
9.
J Appl Physiol (1985) ; 129(5): 1075-1084, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32909920

RESUMO

Positive end-expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondarily to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral hemodynamics in the preterm brain are unknown. We aimed to assess the effect of PEEP on microvessels in the preterm brain by using synchrotron radiation (SR) microangiography, which enables in vivo real-time high-resolution imaging of the cerebral vasculature. Preterm lambs (0.8 gestation, n = 4) were delivered via caesarean section, anesthetized, and ventilated. SR microangiography of the right cerebral hemisphere was performed with iodine contrast administered into the right carotid artery during PEEP ventilation of 5 and 10 cmH2O. Carotid blood flow was measured using an ultrasonic flow probe placed around the left carotid artery. An increase of PEEP from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm) in all four lambs. Additionally, the higher PEEP increased the cerebral contrast transit time in three of the four lambs. Carotid blood flow increased in two lambs, which also had increased carbon dioxide levels during PEEP 10. Our results suggest that PEEP of 10 cmH2O alters the preterm cerebral hemodynamics, with prolonged cerebral blood flow transit and engorgement of small cerebral microvessels likely due to the increased intrathoracic pressure. These microvascular changes are generally not reflected in global assessment of cerebral blood flow or oxygenation.NEW & NOTEWORTHY An increase of positive end-expiratory pressure (PEEP) from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm). This suggests increased intrathoracic pressure due to high PEEP can drive microvessel engorgement in the preterm brain, which may play a role in cerebrovascular injury.


Assuntos
Encéfalo , Circulação Cerebrovascular , Respiração com Pressão Positiva , Síncrotrons , Animais , Encéfalo/efeitos da radiação , Feminino , Pulmão , Perfusão , Gravidez , Ovinos
10.
Radiat Res ; 194(6): 594-599, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991725

RESUMO

In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 µA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of >115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.


Assuntos
Encéfalo/efeitos da radiação , Elétrons , Dosagem Radioterapêutica , Radioterapia/métodos , Criança , Estudos de Viabilidade , Humanos , Método de Monte Carlo , Software
11.
Br J Radiol ; 93(1107): 20190919, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003576

RESUMO

OBJECTIVE: Monte Carlo (MC) simulations substantially improve the accuracy of predicted doses. This study aims to determine and quantify the uncertainties of setting up such a MC system. METHODS: Doses simulated with two Geant4-based MC calculation codes, but independently tuned to the same beam data, have been compared. Different methods of MC modelling of a pre-absorber have been employed, either modifying the beam source parameters (descriptive) or adding the pre-absorber as a physical component (physical). RESULTS: After the independent beam modelling of both systems in water (resulting in excellent range agreement) range differences of up to 3.6/4.8 mm (1.5% of total range) in bone/brain-like tissues were found, which resulted from the use of different mean water ionisation potentials during the energy tuning process. When repeating using a common definition of water, ranges in bone/brain agreed within 0.1 mm and gamma-analysis (global 1%,1mm) showed excellent agreement (>93%) for all patient fields. However, due to a lack of modelling of proton fluence loss in the descriptive pre-absorber, differences of 7% in absolute dose between the pre-absorber definitions were found. CONCLUSION: This study quantifies the influence of using different water ionisation potentials during the MC beam modelling process. Furthermore, when using a descriptive pre-absorber model, additional Faraday cup or ionisation chamber measurements with pre-absorber are necessary. ADVANCES IN KNOWLEDGE: This is the first study quantifying the uncertainties caused by the MC beam modelling process for proton pencil beam scanning, and a more detailed beam modelling process for MC simulations is proposed to minimise the influence of critical parameters.


Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Incerteza , Absorção de Radiação , Ar , Osso e Ossos/efeitos da radiação , Encéfalo/efeitos da radiação , Humanos , Hipofracionamento da Dose de Radiação , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Água
12.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054039

RESUMO

Studies of molecular changes occurred in various brain regions after whole-body irradiation showed a significant increase in terms of the importance in gaining insight into how to slow down or prevent the development of long-term side effects such as carcinogenesis, cognitive impairment and other pathologies. We have analyzed nDNA damage and repair, changes in mitochondrial DNA (mtDNA) copy number and in the level of mtDNA heteroplasmy, and also examined changes in the expression of genes involved in the regulation of mitochondrial biogenesis and dynamics in three areas of the rat brain (hippocampus, cortex and cerebellum) after whole-body X-ray irradiation. Long amplicon quantitative polymerase chain reaction (LA-QPCR) was used to detect nDNA and mtDNA damage. The level of mtDNA heteroplasmy was estimated using Surveyor nuclease technology. The mtDNA copy numbers and expression levels of a number of genes were determined by real-time PCR. The results showed that the repair of nDNA damage in the rat brain regions occurs slowly within 24 h; in the hippocampus, this process runs much slower. The number of mtDNA copies in three regions of the rat brain increases with a simultaneous increase in mtDNA heteroplasmy. However, in the hippocampus, the copy number of mutant mtDNAs increases significantly by the time point of 24 h after radiation exposure. Our analysis shows that in the brain regions of irradiated rats, there is a decrease in the expression of genes (ND2, CytB, ATP5O) involved in ATP synthesis, although by the same time point after irradiation, an increase in transcripts of genes regulating mitochondrial biogenesis is observed. On the other hand, analysis of genes that control the dynamics of mitochondria (Mfn1, Fis1) revealed that sharp decrease in gene expression level occurred, only in the hippocampus. Consequently, the structural and functional characteristics of the hippocampus of rats exposed to whole-body radiation can be different, most significantly from those of the other brain regions.


Assuntos
Encéfalo/efeitos da radiação , Núcleo Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Mitocôndrias/efeitos da radiação , Irradiação Corporal Total/efeitos adversos , Animais , Encéfalo/metabolismo , Núcleo Celular/genética , DNA Mitocondrial/genética , Regulação da Expressão Gênica/efeitos da radiação , Genes Mitocondriais/efeitos da radiação , Masculino , Mitocôndrias/genética , Ratos , Ratos Wistar
13.
J Radiol Prot ; 40(1): 225-242, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31509813

RESUMO

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy-1 to 1 Gy Gy-1) were generally much higher than those for the intracranial irradiations (2.1 µGy Gy-1 to 0.1 Gy Gy-1), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.


Assuntos
Encéfalo/efeitos da radiação , Terapia com Prótons , Radiometria , Coluna Vertebral/efeitos da radiação , Criança , Humanos , Maryland , Modelos Biológicos , Método de Monte Carlo , Neoplasias Induzidas por Radiação/epidemiologia , Lesões por Radiação/epidemiologia , Dosagem Radioterapêutica
15.
Cancer Med ; 9(1): 238-246, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31749325

RESUMO

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.


Assuntos
Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Irradiação Craniana/métodos , Neoplasias Pulmonares/patologia , Transtornos Neurocognitivos/epidemiologia , Lesões por Radiação/epidemiologia , Fatores Etários , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Irradiação Craniana/efeitos adversos , Irradiação Craniana/economia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricos , Pessoa de Meia-Idade , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/etiologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
16.
Health Phys ; 118(2): 136-148, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31634260

RESUMO

The purpose of this study is to support retrospective dose estimation for epidemiological studies by providing estimates of historical absorbed organ doses to the brain, lens of the eye, salivary glands, and thyroid from intraoral dental radiographic examinations performed from 1940 to 2009. We simulated organ doses to an adult over 10 y time periods from 1940 to 2009, based on commonly used sets of x-ray machine settings collected from the literature. Simulations to estimate organ dose were performed using personal computer x-ray Monte Carlo software. Overall, organ doses were less than 1 mGy for a single intraoral radiograph for all decades. From 1940 to 2009, doses to the brain, eye lens, salivary glands, and thyroid decreased by 86, 96, 95, and 89%, respectively. Of these four organs, the salivary glands received the highest doses, with values decreasing from about 0.23 mGy in the 1940s to 0.025 mGy in the 2000s for a single intraoral radiograph. Based on simulations using collected historical data on x-ray technical parameters, improvements in technology and optimization of the technical settings used to perform intraoral dental radiography have resulted in a decrease in absorbed dose to the brain, eye lens, salivary glands, and thyroid over the period from 1940 to 2009.


Assuntos
Encéfalo/efeitos da radiação , Cristalino/efeitos da radiação , Radiografia Dentária , Glândulas Salivares/efeitos da radiação , Glândula Tireoide/efeitos da radiação , Adulto , Humanos , Método de Monte Carlo , Doses de Radiação , Estudos Retrospectivos
17.
Phys Med Biol ; 64(22): 225020, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31374558

RESUMO

The clinical implementation of a variable relative biological effectiveness (RBE) in proton therapy is currently controversially discussed. Initial clinical evidence indicates a variable proton RBE, which needs to be verified. In this study, a radiation response modelling framework for assessing clinical RBE variability is established. It was applied to four selected glioma patients (grade III) treated with adjuvant radio(chemo)therapy and who developed late morphological image changes on T1-weighted contrast-enhanced (T1w-CE) magnetic resonance (MR) images within approximately two years of recurrence-free follow-up. The image changes were correlated voxelwise with dose and linear energy transfer (LET) values using univariable and multivariable logistic regression analysis. The regression models were evaluated by the area-under-the-curve (AUC) method performing a leave-one-out cross validation. The tolerance dose TD50 at which 50% of patient voxels experienced toxicity was interpolated from the models. A Monte Carlo (MC) model was developed to simulate dose and LET distributions, which includes variance reduction (VR) techniques to decrease computation time. Its reliability and accuracy were evaluated based on dose calculations of the clinical treatment planning system (TPS) as well as absolute dose measurements performed in the patient specific quality assurance. Morphological image changes were related to a combination of dose and LET. The multivariable models revealed cross-validated AUC values of up to 0.88. The interpolated TD50 curves decreased with increasing LET indicating an increase in biological effectiveness. The MC model reliably predicted average TPS dose within the clinical target volume as well as absolute water phantom dose measurements within 2% accuracy using dedicated VR settings. The observed correlation of dose and LET with late brain tissue damage suggests considering RBE variability for predicting chronic radiation-induced brain toxicities. The MC model simulates radiation fields in patients precisely and time-efficiently. Hence, this study encourages and enables in-depth patient evaluation to assess the variability of clinical proton RBE.


Assuntos
Método de Monte Carlo , Terapia com Prótons , Eficiência Biológica Relativa , Encéfalo/efeitos da radiação , Humanos , Transferência Linear de Energia , Imagens de Fantasmas , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Planejamento da Radioterapia Assistida por Computador , Reprodutibilidade dos Testes
18.
Neurosurg Focus ; 46(6): E12, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153145

RESUMO

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.


Assuntos
Carbono/uso terapêutico , Irradiação Craniana , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Fótons/uso terapêutico , Terapia com Prótons , Radioterapia Adjuvante/métodos , Alopecia/etiologia , Encéfalo/efeitos da radiação , Cátions/uso terapêutico , Terapia Combinada , Análise Custo-Benefício , Irradiação Craniana/efeitos adversos , Irradiação Craniana/economia , Craniotomia , Seguimentos , Humanos , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Necrose , Prognóstico , Terapia com Prótons/efeitos adversos , Terapia com Prótons/economia , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/economia , Estudos Retrospectivos , Convulsões/etiologia
19.
J Magn Reson Imaging ; 50(4): 1268-1277, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30864193

RESUMO

BACKGROUND: Patients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro-Oncology (RANO) takes a minimum of 4 weeks after the end of treatment. PURPOSE/HYPOTHESIS: To investigate whether chemical exchange saturation transfer (CEST) MRI enables earlier assessment of response to CRT in glioma patients. STUDY TYPE: Longitudinal prospective study. POPULATION: Twelve brain tumor patients who underwent definitive CRT were included in this study. Three longitudinal CEST MRI measurements were performed for each patient at 7T: first before, second immediately after completion of CRT, and a third measurement as a 6-week follow-up. FIELD STRENGTH/SEQUENCE: Conventional MRI (contrast-enhanced, T2 w and diffusion-weighted imaging) at 3T and T2 w and CEST MRI at 7T was performed for all patients. ASSESSMENT: The mean relaxation-compensated relayed nuclear-Overhauser-effect CEST signal (rNOE) and the mean downfield-rNOE-suppressed amide proton transfer (dns-APT) CEST signal were investigated. Additionally, choline-to-N-acetyl-aspartate ratios (Cho/NAA) were evaluated using single-voxel 1 H-MRS in six of these patients. Performance of obtained contrasts was analyzed in assessing treatment response as classified according to the updated RANO criteria. STATISTICAL TEST: Unpaired Student's t-test. RESULTS: The rNOE signal significantly separated stable and progressive disease directly after the end of therapy (post-treatment normalized to pre-treatment mean ± SD: rNOEresponder = 1.090 ± 0.110, rNOEnon-responder = 0.808 ± 0.155, P = 0.015). In contrast, no significant difference was observed between either group when assessing the normalized dns-APT (dns-APTresponder = 0.953 ± 0.384, dns-APTnon-responder = 0.972 ± 0.477, P = 0.95). In the smaller MRS subcohort, normalized Cho/NAA decreased in therapy responders (Cho/NAAresponder = 0.632 ± 0.007, Cho/NAAnon-responder = 0.946 ± 0.124, P = 0.070). DATA CONCLUSION: rNOE mediated CEST imaging at 7T allowed for discrimination of responders and non-responders immediately after the end of CRT, additionally supported by 1 H-MRS data. This is at least 4 weeks earlier than the standard clinical evaluation according to RANO. Therefore, CEST MRI may enable early response assessment in glioma patients. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1268-1277.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Glioma/tratamento farmacológico , Glioma/radioterapia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Aumento da Imagem/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
20.
Pigment Cell Melanoma Res ; 32(4): 553-563, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30767428

RESUMO

BACKGROUND: Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti-PD-1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer-term survivors with MBM treated with this combination. METHODS: Patients with MBM treated with radiotherapy and anti-PD-1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148). RESULTS: From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery. CONCLUSIONS: Radionecrosis is a significant toxicity in longer-term melanoma survivors with MBM treated with anti-PD-1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.


Assuntos
Anticorpos/uso terapêutico , Encéfalo/efeitos da radiação , Melanoma/imunologia , Melanoma/radioterapia , Receptor de Morte Celular Programada 1/imunologia , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/cirurgia , Fatores de Risco , Análise de Sobrevida
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