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  • 1.
    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.

  • 2.
    Larsson, Jakob C.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Laboratory x-ray fluorescence tomography2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    X-ray fluorescence (XRF) tomography is an emerging bio-imaging modality with potential for high-resolution molecular imaging in 3D. 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 XRF tomographysystems 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 (SNR). Other macroscopic biomedical imaging methods provide either structural information with high spatial resolution (e.g., CT) or functional/molecularinformation with lower resolution (e.g., PET).

    In this Thesis we present a laboratory XRF tomography system with high spatial resolution (sub-200 μm), low NP concentration and vastly reduced 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 two photon counting detectors. By using the source’s characteristic 24 keV line emission together with spectrally matched molybdenum NPs the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the NPs, as well as the absorption of the object. An iterative method is used to get aquantitative reconstruction of the XRF image. The reconstructed absorption and XRF images are finally combined into a single 3D overlay image.

    Using this system we have demonstrated high-resolution dual CT and XRF imaging of both phantoms and mice at radiation doses compatible with in vivo small-animal imaging.

  • 3.
    Larsson, Jakob C.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Shaker, Kian
    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.
    Focused anti-scatter grid for background reduction in x-ray fluorescence tomography2018In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 43, no 11, p. 2591-2594Article in journal (Refereed)
    Abstract [en]

    X-ray fluorescence (XRF) tomography is an emerging imaging technology with the potential for high spatial resolution molecular imaging. One of the key limitations is the background noise due to Compton scattering since it degrades the signal and limits the sensitivity. In this Letter, we present a linear focused anti-scatter grid that reduces the Compton scattering background. An anti-scatter grid was manufactured and evaluated both experimentally and theoretically with Monte Carlo simulations. The measurements showed a 31% increase in signal-to-background ratio, and simulations of an improved grid showed that this can easily be extended up to > 75%. Simulated tomographies using the improved grid show a large improvement in reconstruction quality. The anti-scatter grid will be important for in vivo XRF tomography since the background reduction allows for faster scan times, lower doses, and lower nanoparticle concentrations.

  • 4.
    Larsson, Jakob C.
    et al.
    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.
    Vågberg, William
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Toprak, Muhammet
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Dzieran, Johanna
    Arsenian-Henriksson, Marie
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles2018In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 63, p. 164001-Article in journal (Refereed)
    Abstract [en]

    Present macroscopic biomedical imaging methods provide either morphology with high spatial resolution (e.g. CT) or functional/molecular information with lower resolution (e.g. PET). X-ray fluorescence (XRF) from targeted nanoparticles allows molecular or functional imaging but sensitivity has so far been insufficient resulting in low spatial resolution, despite long exposure times and high dose. In the present paper, we show that laboratory XRF tomography with metal-core nanoparticles (NPs) provides a path to functional/molecular biomedical imaging with ~100 µm resolution in living rodents. The high sensitivity and resolution rely on the combination of a high-brightness liquid-metal-jet x-ray source, pencil-beam optics, photon-counting energy-dispersive detection, and spectrally matched NPs. The method is demonstrated on mice for 3D tumor imaging via passive targeting of in-house-fabricated molybdenum NPs. Exposure times, nanoparticle dose, and radiation dose agree well with in vivo imaging.

  • 5.
    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.

  • 6.
    Li, Yuyang
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Shaker, Kian
    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.
    Vogt, Carmen
    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.
    Toprak, Muhammet S.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    A Library of Potential Nanoparticle Contrast Agents for X-Ray Fluorescence Tomography Bioimaging2018In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, article id UNSP 8174820Article in journal (Refereed)
    Abstract [en]

    Nanoparticles (NPs) have been used as contrast agents for several bioimaging modalities. X-ray fluorescence (XRF) tomography can provide sensitive and quantitative 3D detection of NPs. With spectrally matched NPs as contrast agents, we demonstrated earlier in a laboratory system that XRF tomography could achieve high-spatial-resolution tumor imaging in mice. Here, we present the synthesis, characterization, and evaluation of a library of NPs containing Y, Zr, Nb, Rh, and Ru that have spectrally matched K-shell absorption for the laboratory scale X-ray source. The K-shell emissions of these NPs are spectrally well separated from the X-ray probe and the Compton background, making them suitable for the lab-scale XRF tomography system. Their potential as XRF contrast agents is demonstrated successfully in a small-animal equivalent phantom, confirming the simulation results. The diversity in the NP composition provides a flexible platform for a better design and biological optimization of XRF tomography nanoprobes.

  • 7.
    Shaker, Kian
    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.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Quantitative predictions in small-animal X-ray fluorescence tomography2019In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 10, no 8, p. 3773-3788, article id 364926Article in journal (Refereed)
    Abstract [en]

    X-ray fluorescence (XRF) tomography from nanoparticles (NPs) shows promise for high-spatial-resolution molecular imaging in small-animals. Quantitative reconstruction algorithms aim to reconstruct the true distribution of NPs inside the small-animal, but so far there has been no feasible way to predict signal levels or evaluate the accuracy of reconstructions in realistic scenarios. Here we present a GPU-based computational model for small-animal XRF tomography. The unique combination of a highly accelerated Monte Carlo tool combined with an accurate small-animal phantom allows unprecedented realistic full-body simulations. We use this model to simulate our experimental system to evaluate the quantitative performance and accuracy of our reconstruction algorithms on large-scale organs as well as mm-sized tumors. Furthermore, we predict the detection limits for sub-mm tumors at realistic NP concentrations. The computational model will be a valuable tool for optimizing next-generation experimental arrangements and reconstruction algorithms.

  • 8.
    Vågberg, William
    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.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Removal of ring artifacts in microtomography by characterization of scintillator variations2017In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 25, no 19, p. 23191-23198Article in journal (Refereed)
    Abstract [en]

    Ring artifacts reduce image quality in tomography, and arise from faulty detector calibration. In microtomography, we have identified that ring artifacts can arise due to highspatial frequency variations in the scintillator thickness. Such variations are normally removed by a flat-field correction. However, as the spectrum changes, e. g. due to beam hardening, the detector response varies non-uniformly introducing ring artifacts that persist after flat-field correction. In this paper, we present a method to correct for ring artifacts from variations in scintillator thickness by using a simple method to characterize the local scintillator response. The method addresses the actual physical cause of the ring artifacts, in contrary to many other ring artifact removal methods which rely only on image post-processing. By applying the technique to an experimental phantom tomography, we show that ring artifacts are strongly reduced compared to only making a flat-field correction.

1 - 8 of 8
CiteExportLink to result list
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Cite
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  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
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  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
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Output format
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  • asciidoc
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