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Palo Alto, CA, United States

Eggl E.,TU Munich | Schleede S.,TU Munich | Bech M.,TU Munich | Bech M.,Lund University | And 4 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Between X-ray tubes and large-scale synchrotron sources, a large gap in performance exists with respect to the monochromaticity and brilliance of the X-ray beam. However, due to their size and cost, large-scale synchrotrons are not available for more routine applications in small and medium-sized academic or industrial laboratories. This gap could be closed by laser-driven compact synchrotron light sources (CLS), which use an infrared (IR) laser cavity in combination with a small electron storage ring. Hard X-rays are produced through the process of inverse Compton scattering upon the intersection of the electron bunch with the focused laser beam. The produced X-ray beam is intrinsically monochromatic and highly collimated. This makes a CLS well-suited for applications of more advanced - and more challenging - X-ray imaging approaches, such as X-ray multimodal tomography. Here we present, to our knowledge, the first results of a first successful demonstration experiment in which a monochromatic X-ray beam from a CLS was used for multimodal, i.e., phase-, dark-field, and attenuation-contrast, X-ray tomography. We show results from a fluid phantom with different liquids and a biomedical application example in the form of a multimodal CT scan of a small animal (mouse, ex vivo). The results highlight particularly that quantitative multimodal CT has become feasible with laser-driven CLS, and that the results outperform more conventional approaches. © 2015, National Academy of Sciences. All rights reserved. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 6.45M | Year: 2003


Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 649.44K | Year: 2005

DESCRIPTION (provided by applicant): The purpose of this Fast-Track SBIR is to develop an innovative Compact X-ray Station (CXS) for macromolecular crystallography. This station accepts the output x-ray beam of the Compact Light Source, a miniature synchrotron, and delivers x-ray beams to 3 end stations. Each beamline accommodates an integrated commercial diffractometer. Each of 2 side stations receives a tunable, monochromatic x-ray beam in a 30 micron rms spot. The forward station receives a focused higher-flux narrow band x-ray beam. Each of the x-ray beams is tunable from 7 to 16 keV and will provide a flux and energy resolution comparable to synchrotron beamlines. The beamlines can be run separately, in pairs or all 3 simultaneously. In Phase I, we will design the x-ray optics systems and experimentally test a new, tunable focusing monochromator. In Phase II, we will build the x-ray optics and end stations, integrate a commercial diffractometer and fully test the end stations. The CXS is an innovative, powerful, 'turn key' x-ray system which will provide a home laboratory with 3 'synchrotron' beamlines for macromolecular crystallography; 2 beamlines will have the flux, tunability, and energy resolution for single- or multi-wavelength anomalous dispersion experiments, and the third beamline will be optimized for higher-flux screening.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.57M | Year: 2009

DESCRIPTION (provided by applicant): In this Competitive Grant Revision to the Fast-Track SBIR: A Compact X-ray Station for Protein Crystallography (CXS), we describe proposed enhancements and upgrades to the Compact Light Source (CLS) that will result in a substantial increase in x-ray flux to the CXS. The CXS is a project to design and build a combination of x-ray optics, endstations, and software that use the monochromatic, tunable x-ray beam produced by the CLS. The CXS project, though not yet complete, has already resulted in an almost turnkey scientific instrument - a synchrotron-like x-ray system - for structural biologists at academic and corporate research centers. In order to make a significant reduction in data collection time, especially for small crystals, enhancements to the CLS are needed. In response to the NIH Notice: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications - NOT-OD-09-058, we plan to expand the scope of the CXS grant to include several hardware upgrades to the CLS and to fund additional operations time. These efforts will result in significantly more x-ray flux and better reliability of the CLS, which together will greatly improve the impact and performance of the CXS. PUBLIC HEALTH RELEVANCE: The Compact X-ray Station for Protein Crystallography (CXS), along with the Compact Light Source (CLS), provides the technology to bring state-of-the-art macromolecular crystallography to structural biologists in their own local or regional laboratories. This tool will allow a wider community of researchers to conduct a broad range of structure determination experiments that will lead to better understanding of the role of proteins and other macromolecular assemblages involved in disease and therapy.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 1.30M | Year: 2009

DESCRIPTION (provided by applicant): We propose to develop an innovative prototype imaging system which combines the unique properties of the Compact Light Source (a new x-ray source developed with NIGMS SBIR funding) with a new imaging method called Differential Phase Contrast Imaging. This Clinical High Resolution Imaging System (CHRIS) will yield x-ray images which can distinguish subtle variations in soft tissue at an extremely fine scale. The Compact Light Source (CLS), developed with a grant from the Protein Structure Initiative of the NIGMS, is a high-intensity, tunable synchrotron light source that is small enough for clinical implementation. DPCI is an elegant new imaging technology that has demonstrated superior visualization of soft tissue using x-rays. Image contrast for DPCI is caused by the phase shift of x-rays passing through the subject and therefore does not rely upon absorption as with conventional x-ray techniques. The DPCI technique provides three improved contrast mechanisms to reveal specific soft tissue detail not revealed in standard radiographs: higher-quality absorption contrast arising from the nearly monochromatic point-like x-ray source; phase contrast that highlights the density variation of soft tissue; and dark-field contrast which accentuates small-angle scattering from the fine structure of soft tissue. DPCI, as a transmissive technique, also favors high-energy x-rays (30 keV or higher) that can significantly reduce the absorbed dose received by the patient over conventional x-ray techniques. CHRIS is intended to integrate these two innovative technologies-the CLS and DPCI-to produce a turnkey system for both 2-D and tomographic imaging of phantoms and tissue samples with all of the degrees of freedom necessary to simulate the motions required for clinical applications; it will be implemented with the intent of later handling patients without significant re-engineering. When complete, the CHRIS will be a product which will enable the development of clinical applications of this new method towards cancer detection, mammography, osteoarthritis, small animal imaging and other clinical radiological applications which require the detection of fine structure within soft tissue. The CHRIS proposal seeks to develop a new, versatile state-of-the-art instrument to enable both basic biomedical research and clinical investigations of a wide range of health issues. PUBLIC HEALTH RELEVANCE: The proposed Clinical High Resolution Imaging System (CHRIS) will extend the power of present x-ray diagnostic imaging by employing new contrast mechanisms to show extremely fine details within soft tissue that conventional radiography cannot reveal. This improved x-ray imaging would enable researchers to better understand disease and therapies and help to diagnose and treat disease at the earliest detectable stage. CHRIS will be a new state-of-the-art instrument to enable both basic biomedical research and clinical investigations of a wide range of health issues, including the early detection of cancer, in vivo imaging of small animals, as well as other soft tissue applications.

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