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Physics in Medicine and Biology Aug 2022. Irradiation with ultra-high dose rates (>40 Gy s), also known as FLASH irradiation, has the potential to shift the paradigm of radiation therapy because of its reduced...
. Irradiation with ultra-high dose rates (>40 Gy s), also known as FLASH irradiation, has the potential to shift the paradigm of radiation therapy because of its reduced toxicity to normal tissues compared to that of conventional irradiations. The goal of this study was to (1) achieve FLASH irradiation conditions suitable for pre-clinicalandbiology experiments using our synchrotron-based proton beamline and (2) commission the FLASH irradiation conditions achieved.. To achieve these suitable FLASH conditions, we made a series of adaptations to our proton beamline, including modifying the spill length and size of accelerating cycles, repurposing the reference monitor for dose control, and expanding the field size with a custom double-scattering system. We performed the dosimetric commissioning with measurements using an Advanced Markus chamber and EBT-XD films as well as with Monte Carlo simulations.. Through adaptations, we have successfully achieved FLASH irradiation conditions, with an average dose rate of up to 375 Gy s. The Advanced Markus chamber was shown to be appropriate for absolute dose calibration under our FLASH conditions with a recombination factor ranging from 1.002 to 1.006 because of the continuous nature of our synchrotron-based proton delivery within a spill. Additionally, the absolute dose measured using the Advanced Markus chamber and EBT-XD films agreed well, with average and maximum differences of 0.32% and 1.63%, respectively. We also performed a comprehensive temporal analysis for FLASH spills produced by our system, which helped us identify a unique relationship between the average dose rate and the dose in our FLASH irradiation.We have established a synchrotron-based proton FLASH irradiation platform with accurate and precise dosimetry that is suitable for pre-clinical biology experiments. The unique time structure of the FLASH irradiation produced by our synchrotron-based system may shed new light onto the mechanism behind the FLASH effect.
Topics: Proton Therapy; Protons; Radiometry; Radiotherapy Dosage; Synchrotrons
PubMed: 35853442
DOI: 10.1088/1361-6560/ac8269 -
Journal of the Royal Society, Interface Oct 2009The direct detection of biologically relevant metals in single cells and of their speciation is a challenging task that requires sophisticated analytical developments.... (Review)
Review
The direct detection of biologically relevant metals in single cells and of their speciation is a challenging task that requires sophisticated analytical developments. The aim of this article is to present the recent achievements in the field of cellular chemical element imaging, and direct speciation analysis, using proton and synchrotron radiation X-ray micro- and nano-analysis. The recent improvements in focusing optics for MeV-accelerated particles and keV X-rays allow application to chemical element analysis in subcellular compartments. The imaging and quantification of trace elements in single cells can be obtained using particle-induced X-ray emission (PIXE). The combination of PIXE with backscattering spectrometry and scanning transmission ion microscopy provides a high accuracy in elemental quantification of cellular organelles. On the other hand, synchrotron radiation X-ray fluorescence provides chemical element imaging with less than 100 nm spatial resolution. Moreover, synchrotron radiation offers the unique capability of spatially resolved chemical speciation using micro-X-ray absorption spectroscopy. The potential of these methods in biomedical investigations will be illustrated with examples of application in the fields of cellular toxicology, and pharmacology, bio-metals and metal-based nano-particles.
Topics: Biopolymers; Metals; Protons; Spectrometry, X-Ray Emission; Synchrotrons
PubMed: 19605403
DOI: 10.1098/rsif.2009.0166.focus -
Journal of Synchrotron Radiation Jul 2023An in-house designed transmission X-ray microscopy (TXM) instrument has been developed and commissioned at beamline BL18B of the Shanghai Synchrotron Radiation Facility...
An in-house designed transmission X-ray microscopy (TXM) instrument has been developed and commissioned at beamline BL18B of the Shanghai Synchrotron Radiation Facility (SSRF). BL18B is a hard (5-14 keV) X-ray bending-magnet beamline recently built with sub-20 nm spatial resolution in TXM. There are two kinds of resolution mode: one based on using a high-resolution-based scintillator-lens-coupled camera, and the other on using a medium-resolution-based X-ray sCMOS camera. Here, a demonstration of full-field hard X-ray nano-tomography for high-Z material samples (e.g. Au particles, battery particles) and low-Z material samples (e.g. SiO powders) is presented for both resolution modes. Sub-50 nm to 100 nm resolution in three dimensions (3D) has been achieved. These results represent the ability of 3D non-destructive characterization with nano-scale spatial resolution for scientific applications in many research fields.
Topics: Synchrotrons; X-Rays; Silicon Dioxide; China; Tomography, X-Ray
PubMed: 37145138
DOI: 10.1107/S1600577523003168 -
Scientific Reports Sep 2018Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine...
Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline's reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.
Topics: Algorithms; Animals; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Machine Learning; Mice; Synchrotrons; X-Ray Microtomography
PubMed: 30250218
DOI: 10.1038/s41598-018-32628-3 -
Advanced Materials (Deerfield Beach,... Dec 2014In this review, we summarize recent progress in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux... (Review)
Review
In this review, we summarize recent progress in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insights gained from these studies are described and future directions of this field are also discussed.
Topics: Circular Dichroism; Nanostructures; Nucleic Acid Conformation; Nucleic Acids; Photoelectron Spectroscopy; Scattering, Small Angle; Spectrometry, X-Ray Emission; Synchrotrons; X-Ray Absorption Spectroscopy; X-Ray Diffraction
PubMed: 25205057
DOI: 10.1002/adma.201304891 -
Acta Crystallographica. Section D,... Aug 2023Fixed-target crystallography has become a widely used approach for serial crystallography at both synchrotron and X-ray free-electron laser (XFEL) sources. A plethora of...
Fixed-target crystallography has become a widely used approach for serial crystallography at both synchrotron and X-ray free-electron laser (XFEL) sources. A plethora of fixed targets have been developed at different facilities and by various manufacturers, with different characteristics and dimensions and with little or no emphasis on standardization. These many fixed targets have good reasons for their design, shapes, fabrication materials and the presence or absence of apertures and fiducials, reflecting the diversity of serial experiments. Given this, it would be a Sisyphean task to design and manufacture a new standard fixed target that would satisfy all possible experimental configurations. Therefore, a simple standardized descriptor to fully describe fixed targets is proposed rather than a standardized device. This descriptor is a dictionary that could be read by fixed-target beamline software and straightforwardly allow data collection from fixed targets new to that beamline. The descriptor would therefore allow a much easier exchange of fixed targets between sources and facilitate the uptake of new fixed targets, benefiting beamlines, users and manufacturers. This descriptor was first presented at, and was developed following, a meeting of representatives from multiple synchrotron and XFEL sources in Hamburg in January 2023.
Topics: Crystallography, X-Ray; Synchrotrons; Software; Data Collection; Lasers
PubMed: 37463110
DOI: 10.1107/S2059798323005429 -
Physica Medica : PM : An International... Sep 2015Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using... (Review)
Review
Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25-75 micron-wide microplanar beams separated by wider (100-400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.
Topics: Animals; Brain Neoplasms; Dose Fractionation, Radiation; Equipment Design; Evidence-Based Medicine; Humans; Neoplasms; Radiometry; Radiosurgery; Radiotherapy Planning, Computer-Assisted; Radiotherapy, High-Energy; Swine; Synchrotrons; Technology Assessment, Biomedical; Treatment Outcome
PubMed: 26043881
DOI: 10.1016/j.ejmp.2015.04.016 -
Acta Crystallographica. Section D,... May 2021Serial synchrotron crystallography (SSX) is enabling the efficient use of small crystals for structure-function studies of biomolecules and for drug discovery. An...
Serial synchrotron crystallography (SSX) is enabling the efficient use of small crystals for structure-function studies of biomolecules and for drug discovery. An integrated SSX system has been developed comprising ultralow background-scatter sample holders suitable for room and cryogenic temperature crystallographic data collection, a sample-loading station and a humid `gloveless' glovebox. The sample holders incorporate thin-film supports with a variety of designs optimized for different crystal-loading challenges. These holders facilitate the dispersion of crystals and the removal of excess liquid, can be cooled at extremely high rates, generate little background scatter, allow data collection over >90° of oscillation without obstruction or the risk of generating saturating Bragg peaks, are compatible with existing infrastructure for high-throughput cryocrystallography and are reusable. The sample-loading station allows sample preparation and loading onto the support film, the application of time-varying suction for optimal removal of excess liquid, crystal repositioning and cryoprotection, and the application of sealing films for room-temperature data collection, all in a controlled-humidity environment. The humid glovebox allows microscope observation of the sample-loading station and crystallization trays while maintaining near-saturating humidities that further minimize the risks of sample dehydration and damage, and maximize working times. This integrated system addresses common problems in obtaining properly dispersed, properly hydrated and isomorphous microcrystals for fixed-orientation and oscillation data collection. Its ease of use, flexibility and optimized performance make it attractive not just for SSX but also for single-crystal and few-crystal data collection. Fundamental concepts that are important in achieving desired crystal distributions on a sample holder via time-varying suction-induced liquid flows are also discussed.
Topics: Crystallography, X-Ray; Equipment Design; Proteins; Specimen Handling; Synchrotrons
PubMed: 33950019
DOI: 10.1107/S2059798321001868 -
Scientific Reports May 2022X-ray ptychography is a coherent scanning imaging technique widely used at synchrotron facilities for producing quantitative phase images beyond the resolution limit of...
X-ray ptychography is a coherent scanning imaging technique widely used at synchrotron facilities for producing quantitative phase images beyond the resolution limit of conventional x-ray optics. The scanning nature of the technique introduces an inherent overhead to the collection at every scan position and limits the acquisition time of each 2D projection. The overhead associated with motion can be minimised with a continuous-scanning approach. Here we present an acquisition architecture based on continuous-scanning and up-triggering which allows to record ptychographic datasets at up to 9 kHz. We demonstrate the method by applying it to record 2D scans at up to 273 µm/s and 3D scans of a (20 µm) volume in less than three hours. We discuss the current limitations and the outlook toward the development of sub-second 2D acquisition and minutes-long 3D ptychographic tomograms.
Topics: Motion; Optics and Photonics; Synchrotrons; Tomography, X-Ray; X-Rays
PubMed: 35551474
DOI: 10.1038/s41598-022-11292-8 -
Journal of Anatomy Feb 2022The structure of spinal motion segments and spinal vasculature is complicated. Visualizing the three-dimensional (3D) structure of the spine may provide guidance for...
The structure of spinal motion segments and spinal vasculature is complicated. Visualizing the three-dimensional (3D) structure of the spine may provide guidance for spine surgery. However, conventional imaging techniques fail to simultaneously obtain 3D images of soft and hard tissues, and achieving such coimaging states of the spine and its vascular networks remains a challenge. Synchrotron radiation micro-CT (SRμCT) provides a relatively effective and novel method of acquiring detailed 3D information. In this study, specimens of the thoracic spine were obtained from six mice. SRμCT was employed to acquire 3D images of the structure, and histologic staining was performed for comparisons with the SRμCT images. The whole spinal motion segments and the spinal vascular network were simultaneously explored at high resolution. The mean thickness of the cartilaginous end plates (CEPs) and the volume of the intervertebral discs (IVDs) were calculated. The surface of the CEPs and the facet joint cartilage (FJC) were presented as heat maps, which allowed for direct visualization of the thickness distribution. Regional division revealed heterogeneity among the ventral, central, and dorsal parts of the CEPs and between the superior and inferior parts of the facet processes. Moreover, the connections and spatial morphology of the spinal vascular network were visualized. Our study indicates that SRμCT imaging is an ideal method for high-resolution visualization and 3D morphometric analysis of the whole spinal motion segments and spinal vascular network.
Topics: Animals; Imaging, Three-Dimensional; Intervertebral Disc; Mice; Synchrotrons; X-Ray Microtomography; Zygapophyseal Joint
PubMed: 34622448
DOI: 10.1111/joa.13556