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  • 1.
    Burvall, Anna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Stig, Fredrik
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Hallström, Stefan
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Phase-retrieval methods with applications in composite-material tomography2013In: 11th International Conference On X-Ray Microscopy (XRM2012), Institute of Physics Publishing (IOPP), 2013, p. 012015-Conference paper (Refereed)
    Abstract [en]

    In-line phase-contrast x-ray imaging is emerging as a method for observing small details when the contrast in absorption x-ray imaging is low. It gives images with strong edge enhancement, and phase retrieval is necessary to obtain quantitative thickness information. In particular for tomography, clarity can be enhanced by phase retrieval, as here demonstrated on a 3D-weave reinforced composite material. Seven suitable phase-retrieval methods are identified and integrated into a single method, where each version is marked by variations in particular steps. The general method and its variations are outlined and a comparison shows which methods are most suitable in different situations.

  • 2.
    Burvall, Anna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundstrom, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Takman, Per A. C.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Phase retrieval in X-ray phase-contrast imaging suitable for tomography2011In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 19, no 11, p. 10359-10376Article in journal (Refereed)
    Abstract [en]

    In-line phase-contrast X-ray imaging provides images where both absorption and refraction contribute. For quantitative analysis of these images, the phase needs to be retrieved numerically. There are many phase-retrieval methods available. Those suitable for phase-contrast tomography, i.e., non-iterative phase-retrieval methods that use only one image at each projection angle, all follow the same pattern though derived in different ways. We outline this pattern and use it to compare the methods to each other, considering only phase-retrieval performance and not the additional effects of tomographic reconstruction. We also outline derivations, approximations and assumptions, and show which methods are similar or identical and how they relate to each other. A simple scheme for choosing reconstruction method is presented, and numerical phase-retrieval performed for all methods.

  • 3.
    Burvall, Anna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Takman, Per
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Larsson, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    X-ray in-line phase retrieval for tomography2012In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE, SPIE - International Society for Optical Engineering, 2012, Vol. 8313, p. 83136A-Conference paper (Refereed)
    Abstract [en]

    Phase contrast in X-ray imaging offers imaging of fine features at lower doses than absorption. Of the phasecontrast methods in use in-line phase contrast is interesting due to its experimental simplicity, but to extract information on absorption and phase distributions from the resulting images, phase retrieval is needed. Many phase-retrieval methods suitable for different situations have been developed, but few comparisons of those methods done. We consider a sub-group of phase-retrieval methods that are suitable for tomography, i.e., that use only one exposure (for practical experimental reasons) and are non-iterative (for speed). In total we have found seven suitable methods in the literature. All, though derived in different ways under different assumptions, follow the same pattern and can be outlined as a single method where each specific version is marked by variations in particular steps. We summarize this unified approach, and give the variations of the individual methods. In addition, we outline approximations and assumptions of each method. Using this approach it is possible to conclude which specific algorithms are most suitable in specific situations and to test this based on simulated and experimental data. Ultimately, this leads to conclusions on which methods are the most suitable in different situations.

  • 4.
    Hertz, Hans M.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Larsson, Jakob
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Vågberg, William
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Zhou, Tunhe
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Propagation-based phase-contrast imaging with laboratory sources2016In: Optics InfoBase Conference Papers, OSA - The Optical Society , 2016Conference paper (Refereed)
    Abstract [en]

    We demonstrate that propagation-based phase-contrast x-ray imaging with state-of-the art laboratory microfocus sources allows imaging of thick biomedical objects with very high spatial resolution. 

  • 5.
    Hertz, Hans M.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Jakob C.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vogt, Carmen
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Laboratory x-ray fluorescence tomography for high-resolution nanoparticle bio-imaging2014In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 39, no 9, p. 2790-2793Article in journal (Refereed)
    Abstract [en]

    We demonstrate that nanoparticle x-ray fluorescence computed tomography in mouse-sized objects can be performed with very high spatial resolution at acceptable dose and exposure times with a compact laboratory system. The method relies on the combination of the 24 keV line-emission from a high-brightness liquid-metal-jet x-ray source, pencil-beam-forming x-ray optics, photon-counting energy-dispersive detection, and carefully matched (Mo) nanoparticles. Phantom experiments and simulations show that the arrangement significantly reduces Compton background and allows 100 mu m detail imaging at dose and exposure times compatible with small-animal experiments. The method provides a possible path to in vivo molecular x-ray imaging at sub-100 mu m resolution in mice.

  • 6.
    Holmberg, Anders
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Reinspach, Julia
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lindblom, Magnus
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Chubarova, Elena
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Bertilson, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    von Hofsten, Olov
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Nilsson, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Selin, Mårten
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Skoglund Lindberg, Peter
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundstrom, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Takman, Per
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vogt, Ulrich
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Towards 10-nm Soft X-Ray Zone Plate Fabrication2011Conference paper (Refereed)
    Abstract [en]

    In this paper the latest efforts to improve our nanofabrication process for soft x‐ray zone plates is presented. The resolving power, which is proportional to the smallest outermost zone width of the zone plate, is increased by introducing cold development of the electron beam resist that is used for the patterning. With this process we have fabricated Ni zone plates with 13‐nm outermost zone and shown potential for making 11‐nm half‐pitch lines in the electron beam resist. Maintaining the diffraction efficiency of the zone plate is a great concern when the outermost zone width is decreased. To resolve this problem we have developed the so‐called Ni‐Ge zone plate in which the zone plate is build up by Ni and Ge, resulting in an increase of the diffraction efficiency. In a proof‐of‐principle experiment with 25‐nm Ni‐Ge zone plates, we have shown a doubling of the diffraction efficiency. When combined with cold development, the Ni‐Ge process has been shown to work down to 16‐nm half‐pitch. It is plausible that further refinement of the process will make it possible to go to 10‐nm outermost zone widths.

  • 7.
    Larsson, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Small-Animal Imaging with Liquid-Metal-Jet X-Ray Sources2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Small-animal x-ray imaging is an important tool for medical research. The penetration power of x-rays makes it possible to investigate the 3D structure of small animals and other thick biological samples by computed tomography (CT). However, small-animal x-ray imaging often requires high resolution due to the small structures involved, and short exposure times due to sample movement. This constitutes a challenge, since these two properties require compact x-ray sources with parameters that are not widely available.

    In this Thesis we present the first application of liquid-metal-jet sources for small-animal imaging. This source concept was invented at KTH just over ten years ago. The use of a high-speed metal jet as electron-beam target, instead of a solid anode, enables higher x-ray flux while maintaining a small x-ray spot for high-resolution imaging. In the present work, a liquid-metal jet source with a higher-energy spectrum has been developed. It has stronger 24 keV radiation compared to previous sources, which makes it more suitable for imaging of small animals and other few-cm-thick objects, which require the higher penetration of 20-35 keV x-rays.

    We have applied the liquid-metal-jet x-ray sources for whole-body imaging of sacrificed mice and zebrafish. With high-resolution absorption-contrast CT we have visualized fine bone details of mice. We have also used phase contrast, a new method that can considerably improve imaging of, e.g., soft tissue, for demarcation of mm-sized tumors inside a full mouse and for mouse cartilage imaging. In zebrafish imaging, we have exploited the greatly enhanced contrast of phase-imaging to resolve single muscle fibers (and possibly even myofibrils) in whole zebrafish in a laboratory setting for the first time. The muscle structures have diameters in the 5-7 μm range and extremely low contrast, which makes them difficult to observe.

    With phase contrast, we have demonstrated low-dose and high-resolution angiography of mouse and rat organs and tissues ex vivo. We show detection of blood vessels with diameters below 10 μm with radiation doses compatible with living small animals, which is not possible with absorption contrast and iodinated contrast agents. In addition, we have investigated the vascular network of tumors in mouse ears and visualized the chaotic arrangement of newly-formed blood vessels.

    Finally, we present the first results from a new high-power liquid-metal-jet x-ray source prototype, operating at 10× the power of our previous sources, with the same x-ray spot size. This source constitutes an important step towards future in-vivo small-animal laboratory imaging with high resolution.

  • 8.
    Larsson, Daniel H.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Westermark, U.
    Takman, Per
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Arsenian Henriksson, M.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Small-animal tomography with a liquid-metal-jet x-ray source2012In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE, SPIE - International Society for Optical Engineering, 2012, Vol. 8313, p. 83130N-Conference paper (Refereed)
    Abstract [en]

    X-ray tomography of small animals is an important tool for medical research. For high-resolution x-ray imaging of few-cm-thick samples such as, e.g., mice, high-brightness x-ray sources with energies in the few-10-keV range are required. In this paper we perform the first small-animal imaging and tomography experiments using liquid-metal-jet-anode x-ray sources. This type of source shows promise to increase the brightness of microfocus x-ray systems, but present sources are typically optimized for an energy of 9 keV. Here we describe the details of a high-brightness 24-keV electron-impact laboratory microfocus x-ray source based on continuous operation of a heated liquid-In/Ga-jet anode. The source normally operates with 40 W of electron-beam power focused onto the metal jet, producing a 7×7 μm 2 FWHM x-ray spot. The peak spectral brightness is 4 × 10 9 photons/( s × mm 2 × mrad 2 × 0.1%BW) at the 24.2 keV In K α line. We use the new In/Ga source and an existing Ga/In/Sn source for high-resolution imaging and tomography of mice.

  • 9.
    Larsson, Daniel H.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Westermark, Ulrica K.
    Arsenian Henriksson, Marie
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    First application of liquid-metal-jet sources for small-animal imaging: High-resolution CT and phase-contrast tumor demarcation2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 2, p. 021909-Article in journal (Refereed)
    Abstract [en]

    Purpose: Small-animal studies require images with high spatial resolution and high contrast due to the small scale of the structures. X-ray imaging systems for small animals are often limited by the microfocus source. Here, the authors investigate the applicability of liquid-metal-jet x-ray sources for such high-resolution small-animal imaging, both in tomography based on absorption and in soft-tissue tumor imaging based on in-line phase contrast. Methods: The experimental arrangement consists of a liquid-metal-jet x-ray source, the small-animal object on a rotating stage, and an imaging detector. The source-to-object and object-to-detector distances are adjusted for the preferred contrast mechanism. Two different liquid-metal-jet sources are used, one circulating a Ga/In/Sn alloy and the other an In/Ga alloy for higher penetration through thick tissue. Both sources are operated at 40-50 W electron-beam power with similar to 7 mu m x-ray spots, providing high spatial resolution in absorption imaging and high spatial coherence for the phase-contrast imaging. Results: High-resolution absorption imaging is demonstrated on mice with CT, showing 50 mu m bone details in the reconstructed slices. High-resolution phase-contrast soft-tissue imaging shows clear demarcation of mm-sized tumors at much lower dose than is required in absorption. Conclusions: This is the first application of liquid-metal-jet x-ray sources for whole-body small-animal x-ray imaging. In absorption, the method allows high-resolution tomographic skeletal imaging with potential for significantly shorter exposure times due to the power scalability of liquid-metal-jet sources. In phase contrast, the authors use a simple in-line arrangement to show distinct tumor demarcation of few-mm-sized tumors. This is, to their knowledge, the first small-animal tumor visualization with a laboratory phase-contrast system.

  • 10.
    Larsson, Daniel H.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Takman, Per A.C.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    A 24 keV liquid-metal-jet x-ray source for biomedical applications2011In: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 82, no 12, p. 123701-Article in journal (Refereed)
    Abstract [en]

    We present a high-brightness 24-keV electron-impact microfocus x-ray source based on continuous operation of a heated liquid-indium/gallium-jet anode. The 30–70 W electron beam is magnetically focused onto the jet, producing a circular 7–13 μm full width half maximum x-ray spot. The measured spectral brightness at the 24.2 keV In Kα line is 3 × 109 photons/(s × mm2 × mrad2 × 0.1% BW) at 30 W electron-beam power. The high photon energy compared to existing liquid-metal-jet sources increases the penetration depth and allows imaging of thicker samples. The applicability of the source in the biomedical field is demonstrated by high-resolution imaging of a mammography phantom and a phase-contrast angiography phantom.

  • 11.
    Larsson, Daniel H.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics. Stanford University, United States.
    Vågberg, William
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Yaroshenko, Andre
    Yildirim, Ali Oender
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    High-resolution short- exposure small-animal laboratory x-ray phase-contrast tomography2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 39074Article in journal (Refereed)
    Abstract [en]

    X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten mu m spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.

  • 12.
    Larsson, Jakob C.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vågberg, William
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vogt, Carmen
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    High-spatial-resolution nanoparticle X-ray fluorescence tomography2016In: MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING, 2016, article id 97831VConference paper (Refereed)
    Abstract [en]

    X-ray fluorescence tomography (XFCT) has potential for high-resolution 3D molecular x-ray bio-imaging. In this technique the fluorescence signal from targeted nanoparticles (NPs) is measured, providing information about the spatial distribution and concentration of the NPs inside the object. However, present laboratory XFCT systems typically have limited spatial resolution (>1 mm) and suffer from long scan times and high radiation dose even at high NP concentrations, mainly due to low efficiency and poor signal-to-noise ratio. We have developed a laboratory XFCT system with high spatial resolution (sub-100 mu m), low NP concentration and vastly decreased scan times and dose, opening up the possibilities for in-vivo small-animal imaging research. The system consists of a high-brightness liquid-metal-jet microfocus x-ray source, x-ray focusing optics and an energy-resolving photon-counting detector. By using the source's characteristic 24 keV line-emission together with carefully matched molybdenum nanoparticles the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the Mo nanoparticles. A filtered back-projection method is used to produce the final XFCT image.

  • 13.
    Lundström, Ulf
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Scott, L.
    Westermark, U. K.
    Wilhelm, M.
    Henriksson, M. Arsenian
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    X-ray phase-contrast CO2 angiography for sub-10 mu m vessel imaging2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 22, p. 7431-7441Article in journal (Refereed)
    Abstract [en]

    X-ray in-line phase contrast has recently been combined with CO2 angiography for high-resolution small-animal vascular imaging at low radiation dose. In this paper we further investigate the potential and limitations of this method and demonstrate observation of vessels down to 8 mu m in diameter, considerably smaller than the 60 mu m previously reported. Our in-line phase-contrast imaging system is based on a liquid-metal-jet-anode x-ray source and utilizes free-space propagation to convert phase shifts, caused by refractive index variations, into intensity differences. Enhanced refractive index variations are obtained through injection of CO2 gas into the vascular system to replace the blood. We show rat-kidney images with blood vessels down to 27 mu m in diameter and mouse-ear images with vessels down to 8 mu m. The minimum size of observable blood vessels is found to be limited by the penetration of gas into the vascular system and the signal-to-noise ratio, i.e. the allowed dose. The diameters of vessels being gas-filled depend on the gas pressure and follow a simple model based on surface tension. A theoretical signal-to-noise comparison shows that this method requires 1000 times less radiation dose than conventional iodine-based absorption contrast for observing sub-50 mu m vessels.

  • 14.
    Lundström, Ulf
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Takman, Per A. C.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Scott, L.
    Brismar, H.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    X-ray phase contrast for CO2 microangiography2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 9, p. 2603-2617Article in journal (Refereed)
    Abstract [en]

    We demonstrate a laboratory method for imaging small blood vessels using x-ray propagation-based phase-contrast imaging and carbon dioxide (CO2) gas as a contrast agent. The limited radiation dose in combination with CO2 being clinically acceptable makes the method promising for small-diameter vascular visualization. We investigate the possibilities and limitations of the method for small-animal angiography and compare it with conventional absorption-based x-ray angiography. Photon noise in absorption-contrast imaging prevents visualization of blood vessels narrower than 50 mu m at the highest radiation doses compatible with living animals, whereas our simulations and experiments indicate the possibility of visualizing 20 mu m vessels at radiation doses as low as 100 mGy. Experimental computed tomography of excised rat kidney shows blood vessels of diameters down to 60 mu m with improved image quality compared to absorption-based methods. With our present prototype x-ray source, the acquisition time for a tomographic dataset is approximately 1 h, which is long compared to the 1-20 min common for absorption-contrast micro-CT systems. Further development of the liquid-metal-jet microfocus x-ray sources used here and high-resolution x-ray detectors shows promise to reduce exposure times and make this high-resolution method practical for imaging of living animals.

  • 15.
    Lundström, Ulf
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Takman, Per
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Scott, L.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    X-ray phase contrast angiography using CO 2 as contrast agent2012In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE, SPIE - International Society for Optical Engineering, 2012, Vol. 8313, p. 83135J-Conference paper (Refereed)
    Abstract [en]

    We investigate the possibility of using x-ray in-line phase-contrast imaging with gaseous carbon dioxide as contrast agent to visualize small blood vessels. These are difficult to image at reasonable radiation doses using the absorption of conventional iodinated contrast agents. In-line phase contrast is a method for retrieving information on the electron density of the sample as well as the absorption, by moving the detector away from the sample to let phase variations in the transmitted x-rays develop into intensity variations at the detector. Blood vessels are normally difficult to observe in phase contrast even with iodinated contrast agents as the density difference compared to most tissues is small. Carbon dioxide is a clinically accepted x-ray contrast agent. The gas is injected into the blood stream of patients to temporarily displace the blood in a region and thereby reduce the x-ray absorption in the blood vessels. This gives a large density difference which is ideal for phase-contrast imaging. We demonstrate the possibilities of the method by imaging the arterial system of a rat kidney injected with carbon dioxide. Vessels down to 23 ÎŒm in diameter are shown. The method shows potential for live small-animal imaging.

  • 16.
    Lundström, Ulf
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Westermark, U. K.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Small-Animal microangiography using phase-contrast X-ray imaging and gas as contrast agent2014In: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, p. 90331L-Conference paper (Refereed)
    Abstract [en]

    We use propagation-based phase-contrast X-ray imaging with gas as contrast agent To visualize The microvasculature in small animals like mice and rats. The radiation dose required for absorption X-ray imaging is proportional To The minus fourth power of The structure size To be detected. This makes small vessels impossible To image at reasonable radiation doses using The absorption of conventional iodinated contrast agents. Propagation-based phase contrast gives enhanced contrast for high spatial frequencies by moving The detector away from The sample To let phase variations in The Transmitted X-rays develop into intensity variations at The detector. Blood vessels are normally difficult To observe in phase contrast even with iodinated contrast agents as The density difference between blood and most Tissues is relatively small. By injecting gas into The blood stream This density difference can be greatly enhanced giving strong phase contrast. One possible gas To use is carbon dioxide, which is a clinically accepted X-ray contrast agent. The gas is injected into The blood stream of patients To Temporarily displace The blood in a region and Thereby reduce The X-ray absorption in The blood vessels. We have shown That This method can be used To image blood vessels down To 8 μm in diameter in mouse ears. The low dose requirements of This method indicate a potential for live small-Animal imaging and longitudinal studies of angiogenesis.

  • 17.
    Lundström, Ulf
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Westermark, Ulrica K.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Arsenian Henriksson, Marie
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    X-ray phase contrast with injected gas for tumor microangiography2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 11, p. 2801-2811Article in journal (Refereed)
    Abstract [en]

    We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas-tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-mu m-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-mu m-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 mu m vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research.

  • 18. Nachtrab, F.
    et al.
    Firsching, M.
    Speier, C.
    Uhlmann, N.
    Takman, P.
    Tuohimaa, T.
    Heinzl, C.
    Kastner, J.
    Larsson, Daniel
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Holmberg, Anders
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Berti, G.
    Krumm, M.
    Sauerwein, C.
    NanoXCT: Development of a laboratory nano-CT system2014In: Proceedings of SPIE - The International Society for Optical Engineering, 2014Conference paper (Refereed)
    Abstract [en]

    The NanoXCT project aims at developing a laboratory nano-CT system for non-destructive testing applications in the micro- and nano-technology sector. The system concept omits the use of X-ray optics, to be able to provide up to 1 mm FOV (at 285 nm voxel size) and down to 50 nm voxel size (at 0.175 mm FOV) while preserving the flexibility of state-of-the-art micro-CT systems. Within the project a suitable X-ray source, detector and manipulation system are being developed. To cover the demand for elemental analysis, the project will additionally include X-ray spectroscopic techniques. These will be reported elsewhere while this paper is focused on the imaging part of the project. We introduce the system concept including design goals and constraints, and the individual components. We present the current state of the prototype development including first results.

  • 19.
    Vågberg, WIlliam
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Li, Mei
    Arner, Anders
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Laboratory phase-contrast x-ray tomography for imaging of zebrafish muscle structureManuscript (preprint) (Other academic)
  • 20. Zanette, I.
    et al.
    Zhou, Tunhe
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Zdora, M.
    Thibault, P.
    Pfeiffer, F.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Speckle-Based X-Ray Phase-Contrast and Dark-Field Imaging with a Laboratory Source2014In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 112, no 25, p. 253903-Article in journal (Refereed)
    Abstract [en]

    We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.

  • 21.
    Zhou, Tunhe
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Low-dose phase-contrast X-ray imaging: a comparison of two methods2013In: 11th International Conference On X-Ray Microscopy (XRM2012), Institute of Physics (IOP), 2013, p. 012041-Conference paper (Refereed)
    Abstract [en]

    Propagation- and grating-based X-ray phase-contrast imaging methods are compared theoretically. As a prospective application of phase-contrast methods in medical or small animal imaging, carbon dioxide (CO2) angiography is the simulated task. The required dose for the observable blood vessel is compared through simulation. The result indicates that the propagation-based method requires lower dose in this application.

  • 22.
    Zhou, Tunhe
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Thüring, T.
    Rutishauser, S.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Stampanoni, M.
    David, C.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Comparison of propagation-and grating-based x-ray phase-contrast imaging techniques with a liquid-metal-jet source2014In: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, p. 903353-Conference paper (Refereed)
    Abstract [en]

    X-ray phase-contrast imaging has been developed as an alternative to conventional absorption imaging, partly for its dose advantage over absorption imaging at high resolution. Grating-based imaging (GBI) and propagation-based imaging (PBI) are two phase-contrast techniques used with polychromatic laboratory sources. We compare the two methods by experiments and simulations with respect to required dose. A simulation method based on the projection approximation is designed and verified with experiments. A comparison based on simulations of the doses required for detection of an object with respect to its diameter is presented, showing that for monochromatic radiation, there is a dose advantage for PBI for small features but an advantage for GBI at larger features. However, GBI suffers more from the introduction of polychromatic radiation, in this case so much that PBI gives lower dose for all investigated feature sizes. Furthermore, we present and compare experimental images of biomedical samples. While those support the dose advantage of PBI, they also highlight the GBI advantage of quantitative reconstruction of multimaterial samples. For all experiments a liquid-metal-jet source was used. Liquid-metal-jet sources are a promising option for laboratory-based phase-contrast imaging due to the relatively high brightness and small spot size.

  • 23.
    Zhou, Tunhe
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Thüring, Thomas
    Rutishauser, Simon
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Stampanoni, M.
    David, C.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Comparison of two x-ray phase-contrast imaging methods with a microfocus source2013In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 21, no 25, p. 30183-30195Article in journal (Refereed)
    Abstract [en]

    We present a comparison for high-resolution imaging with a laboratory source between grating-based (GBI) and propagation-based (PBI) x-ray phase-contrast imaging. The comparison is done through simulations and experiments using a liquid-metal-jet x-ray microfocus source. Radiation doses required for detection in projection images are simulated as a function of the diameter of a cylindrical sample. Using monochromatic radiation, simulations show a lower dose requirement for PBI for small object features and a lower dose for GBI for larger object features. Using polychromatic radiation, such as that from a laboratory microfocus source, experiments and simulations show a lower dose requirement for PBI for a large range of feature sizes. Tested on a biological sample, GBI shows higher noise levels than PBI, but its advantage of quantitative refractive index reconstruction for multi-material samples becomes apparent.

  • 24.
    Zhou, Tunhe
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Zanette, Irene
    Zdora, Marie-Christine
    Lundström, Ulf
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA.
    Larsson, Daniel H.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Pfeiffer, Franz
    Burvall, Anna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Speckle-based x-ray phase-contrast imaging with a laboratory source and the scanning technique2015In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 40, no 12, p. 2822-2825Article in journal (Refereed)
    Abstract [en]

    The speckle-based scanning method for x-ray phase-contrast imaging is implemented with a liquid-metal-jet source. Using the two-dimensional scanning technique, the phase shift introduced by the object is retrieved in both transverse orientations, and the limitations on spatial resolution inherent to the speckle-tracking technique are avoided. This method opens up possibilities of new high-resolution multimodal applications for lab-based phasecontrast x-ray imaging.

1 - 24 of 24
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