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  • 1.
    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. 

  • 2.
    Häggmark, Ilian
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vågberg, William
    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 quantitative multi-material phase-retrieval algorithms in propagation-based phase-contrast X-ray tomography2017In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 25, no 26, p. 33543-33558Article in journal (Refereed)
    Abstract [en]

    Propagation-based phase-contrast X-ray imaging provides high-resolution, dose-efficient images of biological materials. A crucial challenge is quantitative reconstruction, referred to as phase retrieval, of multi-material samples from single-distance, and hence incomplete, data. In this work, the two most promising methods for multi-material samples, the parallel method, and the linear method, are analytically, numerically, and experimentally compared. Both methods are designed for computed tomography, as they rely on segmentation in the tomographic reconstruction. The methods are found to result in comparable image quality, but the linear method provides faster reconstruction. In addition, as already done for the parallel method, we show that the linear method provides quantitative reconstruction for monochromatic radiation.

  • 3.
    Häggmark, Ilian
    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.
    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.
    Biomedical Applications of Multi-Material Phase Retrieval in Propagation-Based Phase-Contrast Imaging2018In: Microscopy and Microanalysis, Cambridge University Press, 2018, Vol. 24, p. 370-371Conference paper (Refereed)
  • 4.
    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.

  • 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.
    Romell, Jenny
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Häggmark, Ilian
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Twengström, William
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Romell, M.
    Häggman, S.
    Ikram, S.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Virtual histology of dried and mummified biological samples by laboratory phase-contrast tomography2019In: X-Ray Nanoimaging: Instruments and Methods IV, SPIE - International Society for Optical Engineering, 2019, Vol. 11112, article id 111120SConference paper (Refereed)
    Abstract [en]

    Ancient remains from humans, animals and plants hold valuable information about our history. X-ray imaging methods are often, because of their non-destructive nature, used in the analysis of such samples. The classical x-ray imaging methods, radiography and computed tomography (CT), are based on absorption, which works well for radiodense structures like bone, but gives limited contrast for textiles and soft tissues, which exhibit high x-ray transmission. Destructive methods, such as classical histology, have historically been used for analysing ancient soft tissue but the extent to which it is used today is limited because of the fragility and value of many ancient samples. For detailed, non-destructive analysis of ancient biological samples, we instead propose x-ray phase-contrast CT, which like conventional CT gives volume data but with the possibility of better resolution through the detection of phase shift. Using laboratory x-ray sources, we here demonstrate the capabilities of phase-contrast tomography of dried biological samples. Virtual histological analysis of a mummified human hand from ancient Egypt is performed, revealing remains of adipose cells in situ, which would not be possible with classical histology. For higher resolution, a lab-based nano-CT arrangement based on a nanofocus transmission x-ray source is presented. With an x-ray emission spot of 300 nm the system shows potential for sub-micronresolution 3D imaging. For characterisation of the performance of phase-contrast imaging of dried samples a piece of wood is imaged. Finally, we present the first phase-contrast CT data from our nano-CT system, acquired of the dried head of a bee.

  • 7.
    Romell, Jenny
    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.
    Romell, Mikael
    Häggman, Sofia
    Ikram, Salima
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Soft-Tissue Imaging in a Human Mummy: Propagation-based Phase-Contrast CTManuscript (preprint) (Other academic)
  • 8.
    Twengström, William
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    High-resolution biomedical phase-contrast tomography2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Improved three-dimensional biomedical imaging can give a better understanding of tissue structure, growth and diseases. Most present imaging techniques that provide cellular spatial resolution are based on visible or infrared light. These methods cannot image deeper than a millimeter into tissue. Consequently, larger samples cannot be completely imaged without sectioning. Techniques that are typically used to image larger samples don't provide sufficient contrast and resolution to image cellular-sized features in soft tissues. There is a need for new imaging methods that can fill the gap between present methods. For practical reasons, compact equipment is preferred, to enable close connection to other research and applications. Furthermore, minimized sample preparation both reduces the work needed and the time until results are ready.

    In this Thesis, propagation-based phase-contrast tomography with liquid-metal-jet x-ray sources has been investigated for high-resolution three-dimensional biomedical imaging. By using phase contrast, the contrast for cellular-sized features in soft tissue is vastly increased compared to absorption, also in larger samples. The high resolution relies on using an x-ray source with small emission spot, but also with high power to keep exposure times reasonable.

    This Thesis is about developing and optimizing experimental methods and image reconstruction algorithms. A new method to remove ring artifacts was developed and tested, and a comparison of multi-material phase-retrieval algorithms was made. The improvements provide better contrast and resolution, as well as reduce noise and artifacts. The improved image quality is demonstrated in a few biomedical applications. It is shown that the method can image 5 µm large myofibrils in whole-body zebrafish, despite the small size and low contrast of myofibrils. A high-resolution tomography of a mouse can be done fast by using a specialized high-power source. The image quality in tomographies of both human coronary arteries and a mummified human hand is sufficient to analyze the tissues and cellular-sized features, which is something that could be called virtual histology. 

  • 9.
    Twengström, William
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Persson, Jonas
    Szekely, Laszlo
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Physics. 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.
    Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11014Article in journal (Refereed)
    Abstract [en]

    High-spatial-resolution histology of coronary artery autopsy samples play an important role for understanding heart disease such as myocardial infarction. Unfortunately, classical histology is often destructive, has thick slicing, requires extensive sample preparation, and is time-consuming. X-ray micro-CT provides fast nondestructive 3D imaging but absorption contrast is often insufficient, especially for observing soft-tissue features with high resolution. Here we show that propagation-based x-ray phase-contrast tomography has the resolution and contrast to image clinically relevant soft-tissue features in intact coronary artery autopsy samples with cellular resolution. We observe microscopic lipid-rich plaques, individual adipose cells, ensembles of few foam cells, and the thin fibrous cap. The method relies on a small-spot laboratory x-ray microfocus source, and provides high-spatial resolution in all three dimensions, fast data acquisition, minimum sample distortion and requires no sample preparation.

  • 10.
    Vågberg, William
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Larsson, D. H.
    Li, M.
    Arner, A.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    X-ray phase-contrast tomography for high-spatial-resolution zebrafish muscle imaging2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Imaging of muscular structure with cellular or subcellular detail in whole-body animal models is of key importance for understanding muscular disease and assessing interventions. Classical histological methods for high-resolution imaging methods require excision, fixation and staining. Here we show that the three-dimensional muscular structure of unstained whole zebrafish can be imaged with sub-5μm detail with X-ray phase-contrast tomography. Our method relies on a laboratory propagation-based phase-contrast system tailored for detection of low-contrast 4-6μm subcellular myofibrils. The method is demonstrated on 20 days post fertilization zebrafish larvae and comparative histology confirms that we resolve individual myofibrils in the whole-body animal. X-ray imaging of healthy zebrafish show the expected structured muscle pattern while specimen with a dystrophin deficiency (sapje) displays an unstructured pattern, typical of Duchenne muscular dystrophy. The method opens up for whole-body imaging with sub-cellular detail also of other types of soft tissue and in different animal models.

  • 11.
    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)
  • 12.
    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.

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