A first generation compact microbeam radiation therapy system based on carbon nanotube X-ray technology.
Ontology highlight
ABSTRACT:
SUBMITTER: Hadsell M
PROVIDER: S-EPMC3829915 | biostudies-other | 2013 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Microbeam radiation therapy (MRT) is a promising preclinical modality for cancer treatment, with remarkable preferential tumoricidal effects, that is, tumor eradication without damaging normal tissue functions. Significant lifespan extension has been demonstrated in brain tumor-bearing small animals treated with MRT. So far, MRT experiments can only be performed in a few synchrotron facilities around the world. Limited access to MRT facilities prevents this enormously promising radiotherapy technology from reaching the broader biomedical research community and hinders its potential clinical translation. We recently demonstrated, for the first time, the feasibility of generating microbeam radiation in a laboratory environment using a carbon nanotube x-ray source array and performed initial small animal studies with various brain tumor models. This new nanotechnology-enabled microbeam delivery method, although still in its infancy, has shown promise for achieving comparable therapeutic effects to synchrotron MRT and has offered a potential pathway for clinical translation.
| S-EPMC4260778 | biostudies-other
Project description:Microbeam radiation therapy (MRT) is defined as the use of parallel, microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer treatment and brain radiosurgery. Up until now, the possibilities of MRT have mainly been studied using synchrotron sources due to their high flux (100s Gy/s) and approximately parallel x-ray paths. The authors have proposed a compact x-ray based MRT system capable of delivering MRT dose distributions at a high dose rate. This system would employ carbon nanotube (CNT) field emission technology to create an x-ray source array that surrounds the target of irradiation. Using such a geometry, multiple collimators would shape the irradiation from this array into multiple microbeams that would then overlap or interlace in the target region. This pilot study demonstrates the feasibility of attaining a high dose rate and parallel microbeam beams using such a system.The microbeam dose distribution was generated by our CNT micro-CT scanner (100 μm focal spot) and a custom-made microbeam collimator. An alignment assembly was fabricated and attached to the scanner in order to collimate and superimpose beams coming from different gantry positions. The MRT dose distribution was measured using two orthogonal radiochromic films embedded inside a cylindrical phantom. This target was irradiated with microbeams incident from 44 different gantry angles to simulate an array of x-ray sources as in the proposed compact CNT-based MRT system. Finally, phantom translation in a direction perpendicular to the microplanar beams was used to simulate the use of multiple parallel microbeams.Microbeams delivered from 44 gantry angles were superimposed to form a single microbeam dose distribution in the phantom with a FWHM of 300 μm (calculated value was 290 μm). Also, during the multiple beam simulation, a peak to valley dose ratio of ~10 was found when the phantom translation distance was roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to the development of compact MRT technology development was proposed and planned based on the preliminary experimental results presented here and the previous corresponding Monte Carlo simulations.The authors have demonstrated the feasibility of creating microbeam dose distributions at a high dose rate using a proposed compact MRT system. The flexibility of CNT field emission x-ray sources could possibly bring compact and low cost MRT devices to the larger research community and assist in the translational research of this promising new approach to radiation therapy.
| S-EPMC4032446 | biostudies-other
Project description:Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.
| S-EPMC4600606 | biostudies-literature
Project description:Microbeam radiation therapy (MRT) is an experimental radiotherapy technique that has shown potent antitumor effects with minimal damage to normal tissue in animal studies. This unique form of radiation is currently only produced in a few large synchrotron accelerator research facilities in the world. To promote widespread translational research on this promising treatment technology we have proposed and are in the initial development stages of a compact MRT system that is based on carbon nanotube field emission x-ray technology. We report on a Monte Carlo based feasibility study of the compact MRT system design.Monte Carlo calculations were performed using EGSnrc-based codes. The proposed small animal research MRT device design includes carbon nanotube cathodes shaped to match the corresponding MRT collimator apertures, a common reflection anode with filter, and a MRT collimator. Each collimator aperture is sized to deliver a beam width ranging from 30 to 200 μm at 18.6 cm source-to-axis distance. Design parameters studied with Monte Carlo include electron energy, cathode design, anode angle, filtration, and collimator design. Calculations were performed for single and multibeam configurations.Increasing the energy from 100 kVp to 160 kVp increased the photon fluence through the collimator by a factor of 1.7. Both energies produced a largely uniform fluence along the long dimension of the microbeam, with 5% decreases in intensity near the edges. The isocentric dose rate for 160 kVp was calculated to be 700 Gy∕min∕A in the center of a 3 cm diameter target. Scatter contributions resulting from collimator size were found to produce only small (<7%) changes in the dose rate for field widths greater than 50 μm. Dose vs depth was weakly dependent on filtration material. The peak-to-valley ratio varied from 10 to 100 as the separation between adjacent microbeams varies from 150 to 1000 μm.Monte Carlo simulations demonstrate that the proposed compact MRT system design is capable of delivering a sufficient dose rate and peak-to-valley ratio for small animal MRT studies.
| S-EPMC3411585 | biostudies-other
Project description:Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.
| S-EPMC7264143 | biostudies-literature
Project description:Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres. This scoping review was conducted to map the available evidence and provide a comprehensive overview of the similarities, differences, and outcomes of all experiments that have employed animal models in MRT. We considered articles that employed animal models for the purpose of studying the effects of MRT. We searched in seven databases for published and unpublished literature. Two independent reviewers screened citations for inclusion. Data extraction was done by three reviewers. After screening 5688 citations and 159 full-text papers, 95 articles were included, of which 72 were experimental articles. Here we present the animal models and pre-clinical radiation parameters employed in the existing MRT literature according to their use in cancer treatment, non-neoplastic diseases, or normal tissue studies. The study of MRT is concentrated in brain-related diseases performed mostly in rat models. An appropriate comparison between MRT and conventional radiotherapy (instead of synchrotron broad beam) is needed. Recommendations are provided for future studies involving MRT.
| S-EPMC7139755 | biostudies-literature
Project description:A first-generation amperometric galactose biosensor has been systematically developed utilizing layer-by-layer (LbL) construction of xerogels, polymers, and carbon nanotubes toward a greater fundamental understanding of sensor design with these materials and the potential development of a more efficient galactosemia diagnostic tool for clinical application. The effect of several parameters (xerogel silane precursor, buffer pH, enzyme concentration, drying time and the inclusion of a polyurethane (PU) outer layer) on galactose sensitivity were investigated with the critical nature of xerogel selection being demonstrated. Xerogels formed from silanes with medium, aliphatic side chains were shown to exhibit significant enhancements in sensitivity with the addition of PU due to decreased enzyme leaching. Semi-permeable membranes of diaminobenzene and resorcinol copolymer and Nafion were used for selective discrimination against interferent species and the accompanying loss of sensitivity with adding layers was countered using functionalized, single-walled carbon nanotubes (CNTs). Optimized sensor performance included effective galactose sensitivity (0.037 μA/mM) across a useful diagnostic concentration range (0.5 mM to 7 mM), fast response time (~30 s), and low limits of detection (~80 μM) comparable to literature reports on galactose sensors. Additional modification with anionic polymer layers and/or nanoparticles allowed for galactose detection in blood serum samples and additional selectivity effectiveness.
| S-EPMC6359589 | biostudies-literature
Project description:Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose. An increased number of ports and an accumulated valley dose maintained at 10 Gy delayed tumor growth and improved survival. Histopathologically, cell death, vascular damage, and inflammatory response increased in tumors. At identical valley isodose, each additional MRT port extended survival, resulting in an exponential correlation between port numbers and animal lifespan (r2 = 0.9928). A 10 Gy valley dose, in MRT mode, delivered through 5 ports, achieved the same survival as a 25 Gy BB irradiation because of tumor dose hot spots created by intersecting microbeams. Conversely, normal tissue damage remained minimal in all the single converging extratumoral arrays. Multiport MRT reached exceptional ~2.5-fold biological equivalent tumor doses. The unique normal tissue sparing and therapeutic index are eminent prerequisites for clinical translation.
| S-EPMC7956531 | biostudies-literature
Project description:We demonstrate a new optical approach to generate high-frequency (>15?MHz) and high-amplitude focused ultrasound, which can be used for non-invasive ultrasound therapy. A nano-composite film of carbon nanotubes (CNTs) and elastomeric polymer is formed on concave lenses, and used as an efficient optoacoustic source due to the high optical absorption of the CNTs and rapid heat transfer to the polymer upon excitation by pulsed laser irradiation. The CNT-coated lenses can generate unprecedented optoacoustic pressures of >50?MPa in peak positive on a tight focal spot of 75??m in lateral and 400??m in axial widths. This pressure amplitude is remarkably high in this frequency regime, producing pronounced shock effects and non-thermal pulsed cavitation at the focal zone. We demonstrate that the optoacoustic lens can be used for micro-scale ultrasonic fragmentation of solid materials and a single-cell surgery in terms of removing the cells from substrates and neighboring cells.
| S-EPMC3524551 | biostudies-literature
Project description:An optical blackbody is an ideal absorber for all incident optical radiation, and the theoretical study of its radiation spectra paved the way for quantum mechanics (Planck's law). Herein, we propose the concept of an electron blackbody, which is a perfect electron absorber as well as an electron emitter with standard energy spectra at different temperatures. Vertically aligned carbon nanotube arrays are electron blackbodies with an electron absorption coefficient of 0.95 for incident energy ranging from 1 keV to 20 keV and standard electron emission spectra that fit well with the free electron gas model. Such a concept might also be generalized to blackbodies for extreme ultraviolet, X-ray, and γ-ray photons as well as neutrons, protons, and other elementary particles.
| S-EPMC9963611 | biostudies-literature