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1.
J Synchrotron Radiat ; 28(Pt 2): 392-403, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33650550

RESUMO

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale.


Assuntos
Radiometria , Síncrotrons , Método de Monte Carlo , Imagens de Fantasmas , Dosagem Radioterapêutica , Raios X
2.
Phys Med ; 65: 106-113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31450120

RESUMO

PURPOSE: Microbeam radiation therapy is a developing technique that promises superior tumour control and better normal tissue tolerance using spatially fractionated X-ray beams only tens of micrometres wide. Radiochromic film dosimetry at micrometric scale was performed using a microdensitometer, but this instrument presents limitations in accuracy and precision, therefore the use of a microscope is suggested as alternative. The detailed procedures developed to use the two devices are reported allowing a comparison. METHODS: Films were irradiated with single microbeams and with arrays of 50 µm wide microbeams spaced by a 400 µm pitch, using a polychromatic beam with mean energy of 100 keV. The film dose measurements were performed using two independent instruments: a microdensitometer (MDM) and an optical microscope (OM). RESULTS: The mean values of the absolute dose measured with the two instruments differ by less than 5% but the OM provides reproducibility with a standard deviation of 1.2% compared to up to 7% for the MDM. The resolution of the OM was determined to be ~ 1 to 2 µm in both planar directions able to resolve pencil beams irradiation, while the MDM reaches at the best 20 µm resolution along scanning direction. The uncertainties related to the data acquisition are 2.5-3% for the OM and 9-15% for the MDM. CONCLUSION: The comparison between the two devices validates that the OM provides equivalent results to the MDM with better precision, reproducibility and resolution. In addition, the possibility to study dose distributions in two-dimensions over wider areas definitely sanctions the OM as substitute of the MDM.


Assuntos
Dosimetria Fotográfica/instrumentação , Microscopia/instrumentação , Microtecnologia/instrumentação , Dispositivos Ópticos , Calibragem , Processamento de Imagem Assistida por Computador , Razão Sinal-Ruído , Incerteza
3.
Radiat Oncol ; 13(1): 89, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29747666

RESUMO

BACKGROUND: Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time. METHODS: BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 µM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 µm with a center-to-center distance of ≈400 µm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31. RESULTS: After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain. CONCLUSIONS: In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.


Assuntos
Neoplasias Encefálicas/mortalidade , Butionina Sulfoximina/farmacologia , Glioma/mortalidade , Glutationa/metabolismo , Radioterapia/métodos , Síncrotrons , Animais , Antimetabólitos/farmacologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Relação Dose-Resposta à Radiação , Glioma/patologia , Glioma/terapia , Masculino , Projetos Piloto , Ratos , Ratos Endogâmicos F344 , Taxa de Sobrevida
4.
Phys Med ; 32(12): 1795-1800, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27890569

RESUMO

We present here the latest results from tests performed at the ESRF ID17 and ID21 beamlines for the characterization of novel beam monitors for Microbeam Radiation Therapy (MRT), which is currently being implemented at ID17. MRT aims at treating solid tumors by exploiting an array of evenly spaced microbeams, having an energy spectrum distributed between 27 and 600keV and peaking at 100keV. Given the high instantaneous dose delivered (up to 20kGy/s), the position and the intensity of the microbeams has to be precisely and instantly monitored. For this purpose, we developed dedicated silicon microstrip beam monitors. We have successfully characterized them, both with a microbeam array at ID17, and a submicron scanning beam at ID21. We present here the latest results obtained in recent tests along with an outlook on future developments.


Assuntos
Microtecnologia/instrumentação , Radioterapia/instrumentação , Silício , Desenho de Equipamento , Dosagem Radioterapêutica
5.
Phys Med Biol ; 61(14): N349-61, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27366861

RESUMO

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency's TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called 'current ramping' method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.


Assuntos
Fracionamento da Dose de Radiação , Radiometria/métodos , Síncrotrons/instrumentação , Água/química , Humanos , Raios X
6.
Phys Med ; 31(6): 615-20, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25936621

RESUMO

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.


Assuntos
Fracionamento da Dose de Radiação , Lesões por Radiação/prevenção & controle , Proteção Radiológica/métodos , Radioterapia de Alta Energia/efeitos adversos , Pele/lesões , Pele/efeitos da radiação , Animais , Materiais Biomiméticos/efeitos da radiação , Desenho de Equipamento , Medicina Baseada em Evidências , Humanos , Tratamentos com Preservação do Órgão/métodos , Terapia com Prótons/efeitos adversos , Prótons , Lesões por Radiação/etiologia , Valores de Referência , Pele/patologia , Síncrotrons , Avaliação da Tecnologia Biomédica , Resultado do Tratamento
7.
Phys Med ; 31(6): 607-14, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25934524

RESUMO

Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.


Assuntos
Relógios Biológicos , Fracionamento da Dose de Radiação , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Radiocirurgia/instrumentação , Síncrotrons/instrumentação , Animais , Desenho de Equipamento , Estudos de Viabilidade , Hipocampo/fisiopatologia , Hipocampo/efeitos da radiação , Hipocampo/cirurgia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/fisiopatologia , Rede Nervosa/cirurgia , Radiocirurgia/métodos , Radioterapia de Alta Energia/instrumentação , Radioterapia de Alta Energia/métodos , Ratos , Resultado do Tratamento
8.
Phys Med ; 31(6): 564-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25773883

RESUMO

Microbeam radiation therapy (MRT), a novel form of spatially fractionated radiotherapy (RT), uses arrays of synchrotron-generated X-ray microbeams (MB). MRT has been identified as a promising treatment concept that might be applied to patients with malignant central nervous system (CNS) tumours for whom, at the current stage of development, no satisfactory therapy is available yet. Preclinical experimental studies have shown that the CNS of healthy rodents and piglets can tolerate much higher radiation doses delivered by spatially separated MBs than those delivered by a single, uninterrupted, macroscopically wide beam. High-dose, high-precision radiotherapies such as MRT with reduced probabilities of normal tissue complications offer prospects of improved therapeutic ratios, as extensively demonstrated by results of experiments published by many international groups in the last two decades. The significance of developing MRT as a new RT approach cannot be understated. Up to 50% of cancer patients receive conventional RT, and any new treatment that provides better tumour control whilst preserving healthy tissue is likely to significantly improve patient outcomes.


Assuntos
Neoplasias Encefálicas/radioterapia , Fracionamento da Dose de Radiação , Radioterapia de Alta Energia/instrumentação , Radioterapia de Alta Energia/métodos , Síncrotrons/instrumentação , Animais , Desenho de Equipamento , Medicina Baseada em Evidências , Humanos , Camundongos , Ratos , Suínos , Avaliação da Tecnologia Biomédica , Resultado do Tratamento
9.
Mutat Res ; 704(1-3): 160-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20034592

RESUMO

Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has yielded many results from preclinical trials based on different animal models, including mice, rats, piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100 microm wide) microplanar beams separated by wider (100-400 microm centre-to-centre) microplanar spaces. The height of these microbeams typically varies from 1 to 100 mm, depending on the target and the desired preselected field size to be irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues, up to approximately 2 yr after irradiation, and at the same time show a preferential damage of malignant tumor tissues; these effects of MRT have now been extensively studied over nearly two decades. More recently, some biological in vivo effects of synchrotron X-ray beams in the millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may differ to some extent from those of microscopic beams, have been followed up to approximately 7 months after irradiation. Comparisons between broad-beam irradiation and MRT indicate a higher tumor control for the same sparing of normal tissue in the latter, even if a substantial fraction of tumor cells are not receiving a radiotoxic level of radiation. The hypothesis of a selective radiovulnerability of the tumor vasculature versus normal blood vessels by MRT, and of the cellular and molecular mechanisms involved remains under investigation. The paper highlights the history of MRT including salient biological findings after microbeam irradiation with emphasis on the vascular components and the tolerance of the central nervous system. Details on experimental and theoretical dosimetry of microbeams, core issues and possible therapeutic applications of MRT are presented.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Radioterapia/métodos , Síncrotrons , Tecnologia Radiológica/métodos , Raios X , Animais , Vasos Sanguíneos/efeitos da radiação , Neoplasias Encefálicas/irrigação sanguínea , Fracionamento da Dose de Radiação , História do Século XX , História do Século XXI , Humanos , Neoplasias/irrigação sanguínea , Radiometria , Radioterapia/instrumentação , Tecnologia Radiológica/história
10.
Rev Sci Instrum ; 80(7): 074301, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19655968

RESUMO

During the past decade microbeam radiation therapy has evolved from preclinical studies to a stage in which clinical trials can be planned, using spatially fractionated, highly collimated and high intensity beams like those generated at the x-ray ID17 beamline of the European Synchrotron Radiation Facility. The production of such microbeams typically between 25 and 100 microm full width at half maximum (FWHM) values and 100-400 microm center-to-center (c-t-c) spacings requires a multislit collimator either with fixed or adjustable microbeam width. The mechanical regularity of such devices is the most important property required to produce an array of identical microbeams. That ensures treatment reproducibility and reliable use of Monte Carlo-based treatment planning systems. New high precision wire cutting techniques allow the fabrication of these collimators made of tungsten carbide. We present a variable slit width collimator as well as a single slit device with a fixed setting of 50 microm FWHM and 400 microm c-t-c, both able to cover irradiation fields of 50 mm width, deemed to meet clinical requirements. Important improvements have reduced the standard deviation of 5.5 microm to less than 1 microm for a nominal FWHM value of 25 microm. The specifications of both devices, the methods used to measure these characteristics, and the results are presented.


Assuntos
Microtecnologia/instrumentação , Radioterapia/instrumentação , Modelos Lineares , Temperatura
11.
Med Phys ; 36(4): 1128-37, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19472618

RESUMO

Various dosimeters have been tested for assessing absorbed doses with microscopic spatial resolution in targets irradiated by high-flux, synchrotron-generated, low-energy (approximately 30-300 keV) x-ray microbeams. A MOSFET detector has been used for this study since its radio sensitive element, which is extraordinarily narrow (approximately 1 microm), suits the main applications of interest, microbeam radiation biology and microbeam radiation therapy (MRT). In MRT, micrometer-wide, centimeter-high, and vertically oriented swaths of tissue are irradiated by arrays of rectangular x-ray microbeams produced by a multislit collimator (MSC). We used MOSFETs to measure the dose distribution, produced by arrays of x-ray microbeams shaped by two different MSCs, in a tissue-equivalent phantom. Doses were measured near the center of the arrays and maximum/minimum (peak/valley) dose ratios (PVDRs) were calculated to determine how variations in heights and in widths of the microbeams influenced this for the therapy, potentially important parameter. Monte Carlo (MC) simulations of the absorbed dose distribution in the phantom were also performed. The results show that when the heights of the irradiated swaths were below those applicable to clinical therapy (< 1 mm) the MC simulations produce estimates of PVDRs that are up to a factor of 3 higher than the measured values. For arrays of higher microbeams (i.e., 25 microm x 1 cm instead of 25 x 500 microm2), this difference between measured and simulated PVDRs becomes less than 50%. Closer agreement was observed between the measured and simulated PVDRs for the Tecomet MSC (current collimator design) than for the Archer MSC. Sources of discrepancies between measured and simulated doses are discussed, of which the energy dependent response of the MOSFET was shown to be among the most important.


Assuntos
Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/instrumentação , Síncrotrons , Calibragem , Simulação por Computador , Desenho de Equipamento , Humanos , Modelos Estatísticos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Radiometria/instrumentação , Radioterapia/instrumentação , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Raios X
12.
Med Phys ; 34(11): 4322-30, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18072497

RESUMO

Theoretical dose distributions for microbeam radiation therapy (MRT) are computed in this paper using the GEANT4 Monte Carlo (MC) simulation toolkit. MRT is an innovative experimental radiotherapy technique carried out using an array of parallel microbeams of synchrotron-wiggler-generated x rays. Although the biological mechanisms underlying the effects of microbeams are still largely unknown, the effectiveness of MRT can be traced back to the natural ability of normal tissues to rapidly repair small damages to the vasculature, and on the lack of a similar healing process in tumoral tissues. Contrary to conventional therapy, in which each beam is at least several millimeters wide, the narrowness of the microbeams allows a rapid regeneration of the blood vessels along the beams' trajectories. For this reason the calculation of the "valley" dose is of crucial importance and the correct use of MC codes for such purposes must be understood. GEANT4 offers, in addition to the standard libraries, a specialized package specifically designed to deal with electromagnetic interactions of particles with matter for energies down to 250 eV. This package implements two different approaches for electron and photon transport, one based on evaluated data libraries, the other adopting analytical models. These features are exploited to cross-check theoretical computations for MRT. The lateral and depth dose profiles are studied for the irradiation of a 20 cm diameter, 20 cm long cylindrical phantom, with cylindrical sources of different size and energy. Microbeam arrays are simulated with the aid of superposition algorithms, and the ratios of peak-to-valley doses are computed for typical cases used in preclinical assays. Dose profiles obtained using the GEANT4 evaluated data libraries and analytical models are compared with simulation results previously obtained using the PENELOPE code. The results show that dose profiles computed with GEANT4's analytical model are almost indistinguishable from those obtained with the PENELOPE code, but some noticeable differences appear when the evaluated data libraries are used.


Assuntos
Radiometria/instrumentação , Radiometria/métodos , Algoritmos , Animais , Simulação por Computador , Humanos , Modelos Biológicos , Método de Monte Carlo , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador , Espalhamento de Radiação , Software
13.
Med Phys ; 33(9): 3248-59, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17022219

RESUMO

Microbeam radiation therapy (MRT) is being performed by using an array of narrow rectangular x-ray beams (typical beam sizes 25 microm X 1 cm), positioned close to each other (typically 200 microm separation), to irradiate a target tissue. The ratio of peak-to-valley doses (PVDR's) in the composite dose distribution has been found to be strongly correlated with the normal tissue tolerance and the therapeutic effect of MRT. In this work a Monte Carlo (MC) study of the depth- and lateral-dose profiles in water for single x-ray microbeams of different shapes and energies has been performed with the MC code PENELOPE. The contributions to the dose deposition from different interaction types have been determined at different distances from the center of the microbeam. The dependence of the peak dose, in a water phantom, on the microbeam field size used in the preclinical trials, has been demonstrated. Composite dose distributions for an array of microbeams were obtained using superposition algorithms and PVDR's were determined and compared with literature results obtained with other Monte Carlo codes. The dependence of the PVDR's on microbeam width, x-ray energy used, and on the separation between adjacent microbeams has been studied in detail.


Assuntos
Algoritmos , Modelos Biológicos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Carga Corporal (Radioterapia) , Simulação por Computador , Humanos , Modelos Estatísticos , Método de Monte Carlo , Dosagem Radioterapêutica , Radioterapia Conformacional/instrumentação , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
J Neurooncol ; 78(2): 135-43, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16598429

RESUMO

PURPOSE: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares the developing CNS and other normal tissues, is tolerated well by developing animals and palliates advanced 9LGS tumors. This report, to our knowledge, is the first demonstration that gene-mediated immunotherapy (GMIMPR) enhances the efficacy of MRT for advanced 9LGS tumors. METHODS: Seventy-six male Fischer 344 rats were implanted ic with 10(4)9LGS cells on d0. By d14, the cells had generated approximately approximately 40 mm3 ic 9LGS tumours, experimental models for therapy of moderately aggressive human malignant astrocytomas. Each of the 14 untreated (control) rats died from a large (>100 mg) ic tumor before d29 (median, d21). On d14, the remaining 62 rats were given deliberately suboptimal microbeam radiation therapy (MRT) by a single lateral exposure of the tumor-bearing zone of the head to a 10.1 mm-wide, approximately approximately 11 mm-high array of 20-39 microm-wide, nearly parallel beams of synchrotron wiggler-generated radiation (mainly approximately 50-150 keV X-rays) that delivered 625 Gy peak skin doses at approximately approximately 211 microm ctc intervals in approximately approximately 300 ms either without additional treatments (MRT-only, 25 rats), with post-MRT GMIMPR (MRT+GMIMPR, 23 rats: multiple sc injections of irradiated (clonogenically-disabled) GM-CSF gene-transfected 9LGS cells), or with post-MRT IMPR (MRT+IMPR, 14 rats: multiple sc injections of irradiated (clonogenically-disabled) 9LGS cells. RESULTS: The median post-implantation survivals of rats in the MRT-only, MRT+GMIMPR and MRT+IMPR groups were over twice that of controls; further, approximately approximately 20% of rats in MRT-only and MRT+IMPR groups survived >1 yr with no obvious disabilities. Moreover, over 40% of MRT+GMIMPR rats survived >1 yr with no obvious disabilities, a significant (P<0.04) increase over the MRT-only and MRT+IMPR groups. SIGNIFICANCE: These data suggest that the combination of MRT+GMIMPR might be better than MRT only for unifocal CNS tumors, particularly in infants and young children.


Assuntos
Neoplasias Encefálicas/terapia , Gliossarcoma/terapia , Imunoterapia/métodos , Radiocirurgia/métodos , Fatores Etários , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/cirurgia , Terapia Combinada/métodos , Terapia Genética , Gliossarcoma/imunologia , Gliossarcoma/cirurgia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Imunização , Masculino , Dosagem Radioterapêutica , Ratos , Ratos Endogâmicos F344 , Estatísticas não Paramétricas , Análise de Sobrevida , Transfecção
15.
Br J Radiol ; 79(937): 71-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16421408

RESUMO

Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two orthogonal exposures with or without a 16 mm aluminium filter through a multislit collimator (MSC) by arrays of nearly parallel microbeams spaced 200 microm on centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy, or 884 Gy from 35 microm wide beams or 442 Gy from 70 microm wide beams. The 442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day median survival times (MST) (post-irradiation), respectively, exceeding the 20 day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Radiocirurgia/métodos , Síncrotrons , Animais , Feminino , Humanos , Extremidade Inferior , Camundongos , Camundongos Endogâmicos C3H , Modelos Animais , Transplante de Neoplasias , Cuidados Paliativos , Taxa de Sobrevida
16.
Phys Med Biol ; 50(13): 3103-11, 2005 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-15972983

RESUMO

Microbeam radiation therapy (MRT) has the potential to treat infantile brain tumours when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of x-rays but provides unusual resistance to radioneurotoxicity, presumably from the migration of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated microslices of tissues. We present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumour area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumouricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumour in the paths of the arrays.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Encéfalo/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Animais , Estudos de Viabilidade , Doses de Radiação , Lesões por Radiação/prevenção & controle , Ratos , Resultado do Tratamento
17.
Med Phys ; 30(4): 583-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12722810

RESUMO

Preclinical experiments are carried out with approximately 20-30 microm wide, approximately 10 mm high parallel microbeams of hard, broad-"white"-spectrum x rays (approximately 50-600 keV) to investigate microbeam radiation therapy (MRT) of brain tumors in infants for whom other kinds of radiotherapy are inadequate and/or unsafe. Novel physical microdosimetry (implemented with MOSFET chips in the "edge-on" mode) and Monte Carlo computer-simulated dosimetry are described here for selected points in the peak and valley regions of a microbeam-irradiated tissue-equivalent phantom. Such microbeam irradiation causes minimal damage to normal tissues, possible because of rapid repair of their microscopic lesions. Radiation damage from an array of parallel microbeams tends to correlate with the range of peak-valley dose ratios (PVDR). This paper summarizes comparisons of our dosimetric MOSFET measurements with Monte Carlo calculations. Peak doses at depths <22 mm are 18% less than Monte Carlo values, whereas those depths >22 mm and valley doses at all depths investigated (2 mm-62 mm) are within 2-13% of the Monte Carlo values. These results lend credence to the use of MOSFET detector systems in edge-on mode for microplanar irradiation dosimetry.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/radioterapia , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia/instrumentação , Rombencéfalo/fisiopatologia , Transdutores , Animais , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Europa (Continente) , Humanos , Recém-Nascido , Miniaturização , Modelos Biológicos , Serviço Hospitalar de Medicina Nuclear , Radiometria/métodos , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Semicondutores , Sensibilidade e Especificidade , Síncrotrons
18.
Cell Mol Biol (Noisy-le-grand) ; 46(6): 1053-63, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10976863

RESUMO

The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy is progressing. This paper will present a very brief overview of the beamline and the imaging and therapy programs.


Assuntos
Síncrotrons/instrumentação , Animais , Angiografia Coronária/instrumentação , Europa (Continente) , Humanos , Radioterapia de Alta Energia/instrumentação , Pesquisa , Tomografia Computadorizada por Raios X/instrumentação , Difração de Raios X/instrumentação
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