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Kördel, M., Fogelqvist, E., Carannante, V., Önfelt, B., Reddy, H. K. N., Svenda, M., . . . Hertz, H. (2019). Biological Laboratory X-Ray Microscopy. In: Lai, B Somogyi, A (Ed.), X-Ray Nanoimaging: Instruments and Methods IV. Paper presented at X-Ray Nanoimaging: Instruments and Methods IV 2019; San Diego; United States; 11 August 2019 through 12 August 2019. SPIE - International Society for Optical Engineering, 11112, Article ID 111120T.
Open this publication in new window or tab >>Biological Laboratory X-Ray Microscopy
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2019 (English)In: X-Ray Nanoimaging: Instruments and Methods IV / [ed] Lai, B Somogyi, A, SPIE - International Society for Optical Engineering, 2019, Vol. 11112, article id 111120TConference paper, Published paper (Refereed)
Abstract [en]

Zone-plate-based soft x-ray microscopes operating in the water window allow high-resolution and high-contrast imaging of intact cells in their near-native state. Laboratory-source-based x-ray microscopes are an important complement to the accelerator-based instruments, providing high accessibility and allowing close integration with other cell-biological techniques. Here we present recent biological applications using the Stockholm laboratory water-window x-ray microscope, which is based on a liquid-nitrogen-jet laser-plasma source. Technical improvements to the microscope in the last few years have resulted in increased x-ray flux at the sample and significantly improved stability and reliability. In addition to this, vibrations in key components have been measured, analyzed and reduced to improve the resolution to 25 nm half-period. The biological applications include monitoring the development of carbon-dense vesicles in starving human embryonic kidney cells (HEK293T), imaging the interaction between natural killer (NK) cells and HEK293T target cells, and most recently studying a newly discovered giant DNA virus and the process of viral replication inside a host amoeba. All biological imaging was done on cryo-frozen hydrated samples in 2D and in some cases 3D.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2019
Series
Proceedings of SPIE, ISSN 0277-786X ; 11112
Keywords
X-ray microscopy, water-window, laboratory, resolution, cell imaging, cryo
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-268787 (URN)10.1117/12.2531165 (DOI)000511110600017 ()2-s2.0-85076560867 (Scopus ID)978-1-5106-2918-9 (ISBN)
Conference
X-Ray Nanoimaging: Instruments and Methods IV 2019; San Diego; United States; 11 August 2019 through 12 August 2019
Note

QC 20200224

Available from: 2020-02-24 Created: 2020-02-24 Last updated: 2020-02-24Bibliographically approved
Romell, J., Häggmark, I., Twengström, W., Romell, M., Häggman, S., Ikram, S. & Hertz, H. (2019). Virtual histology of dried and mummified biological samples by laboratory phase-contrast tomography. In: X-Ray Nanoimaging: Instruments and Methods IV. Paper presented at X-Ray Nanoimaging: Instruments and Methods IV 2019; San Diego; United States; 11 August 2019 through 12 August 2019. SPIE - International Society for Optical Engineering, 11112, Article ID 111120S.
Open this publication in new window or tab >>Virtual histology of dried and mummified biological samples by laboratory phase-contrast tomography
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2019 (English)In: X-Ray Nanoimaging: Instruments and Methods IV, SPIE - International Society for Optical Engineering, 2019, Vol. 11112, article id 111120SConference paper, Published 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.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2019
Series
Proceedings of SPIE - The International Society for Optical Engineering, ISSN 0277-786X ; 11112
Keywords
Archaeology, Liquid-metal-jet x-ray source, Mummy, Nanofocus x-ray source, Phase-contrast tomography, Virtual histology
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-266659 (URN)10.1117/12.2531163 (DOI)000511110600016 ()2-s2.0-85076557974 (Scopus ID)9781510629172 (ISBN)
Conference
X-Ray Nanoimaging: Instruments and Methods IV 2019; San Diego; United States; 11 August 2019 through 12 August 2019
Note

QC 20200116

Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2020-02-21Bibliographically approved
Twengström, W., Persson, J., Szekely, L. & Hertz, H. (2018). Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography. Scientific Reports, 8, Article ID 11014.
Open this publication in new window or tab >>Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11014Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-232889 (URN)10.1038/s41598-018-29344-3 (DOI)000439278300049 ()30030461 (PubMedID)2-s2.0-85050531102 (Scopus ID)
Note

QC 20180809

Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-09-06Bibliographically approved
Häggmark, I., Romell, J., Lewin, S., Öhman, C. & Hertz, H. (2018). Cellular-Resolution Imaging of Microstructures in Rat Bone using Laboratory Propagation-Based Phase-Contrast X-ray Tomography. In: Microscopy and Microanalysis: . Paper presented at 14th International Conference on X-ray Microscopy (pp. 368-369). , 24
Open this publication in new window or tab >>Cellular-Resolution Imaging of Microstructures in Rat Bone using Laboratory Propagation-Based Phase-Contrast X-ray Tomography
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2018 (English)In: Microscopy and Microanalysis, 2018, Vol. 24, p. 368-369Conference paper, Published paper (Refereed)
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-240273 (URN)10.1017/S1431927618014137 (DOI)
Conference
14th International Conference on X-ray Microscopy
Note

QC 20181217

Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2019-12-20Bibliographically approved
Larsson, J. C., Shaker, K. & Hertz, H. (2018). Focused anti-scatter grid for background reduction in x-ray fluorescence tomography. Optics Letters, 43(11), 2591-2594
Open this publication in new window or tab >>Focused anti-scatter grid for background reduction in x-ray fluorescence tomography
2018 (English)In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 43, no 11, p. 2591-2594Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
OPTICAL SOC AMER, 2018
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-230827 (URN)10.1364/OL.43.002591 (DOI)000433963300043 ()29856437 (PubMedID)2-s2.0-85048058307 (Scopus ID)
Note

QC 20180619

Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-10-16Bibliographically approved
Larsson, J. C., Vogt, C., Vågberg, W., Toprak, M., Dzieran, J., Arsenian-Henriksson, M. & Hertz, H. (2018). High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles. Physics in Medicine and Biology, 63, 164001
Open this publication in new window or tab >>High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles
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2018 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 63, p. 164001-Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2018
Keywords
x-ray, x-ray fluorescence, tomography, nanoparticles
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-233331 (URN)10.1088/1361-6560/aad51e (DOI)000441712300001 ()30033936 (PubMedID)2-s2.0-85052501337 (Scopus ID)
Funder
Swedish Research CouncilWallenberg Foundations
Note

QC 20180828

Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2020-03-09Bibliographically approved
Romell, J., Vagberg, W., Romell, M., Haggman, S., Ikram, S. & Hertz, H. (2018). Soft-Tissue Imaging in a Human Mummy: Propagation-based Phase-Contrast CT. Radiology, 289(3), 670-676
Open this publication in new window or tab >>Soft-Tissue Imaging in a Human Mummy: Propagation-based Phase-Contrast CT
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2018 (English)In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 289, no 3, p. 670-676Article in journal (Refereed) Published
Abstract [en]

Purpose: To evaluate phase-contrast CT as a noninvasive alternative to histology in the study of ancient soft tissue. Materials and Methods: The imaging was performed between May 8 and June 13, 2017. A mummified human hand from ancient Egypt was imaged in a laboratory phase-contrast CT arrangement with propagation-based imaging. The experimental arrangement for propagation-based imaging included a microfocus x-ray source, a rotation stage for the sample, and an x-ray detector. The mummified hand was imaged in two different modes. First, a CT scan of the whole hand was performed in an overview arrangement. Then, a detailed scan of the tip of the middle finger was performed. With imaging distances tailored fora large magnification and to maximize die phase-contrast signal, the estimated resolution in the final images was 6-9 mu m. Results: The overview CT allowed identification tendons of the hand, as well as identification of arteries and nerves in the dehydrated soft tissue. In the detailed phase-contrast setting, virtual histology of the soft tissues of the fingertip could be performed. Blood vessels in the nail bed and the microanatomy of the bone marrow and hypodermis were imaged, and the layers of the skin could be distinguished. Round structures in the adipose tissue were identified as the reamins of adipocytes. Conclusion: Laboratory phase-contrast CT enables imaging of the anatomy and microanatomy of mummified soft tissue with sub-10-mu m resolution and may serve as a complement or alternative to the classic invasive histrologic methods used in soft-tissue paleopathology. (C) RSNA.2018

Place, publisher, year, edition, pages
RADIOLOGICAL SOC NORTH AMERICA, 2018
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-239987 (URN)10.1148/radiol.2018180945 (DOI)000450569200015 ()30251933 (PubMedID)2-s2.0-85056714548 (Scopus ID)
Funder
Swedish Research CouncilWallenberg Foundations
Note

QC 20181211

Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-11Bibliographically approved
Häggmark, I., Vågberg, W., Hertz, H. & Burvall, A. (2017). Comparison of quantitative multi-material phase-retrieval algorithms in propagation-based phase-contrast X-ray tomography. Optics Express, 25(26), 33543-33558
Open this publication in new window or tab >>Comparison of quantitative multi-material phase-retrieval algorithms in propagation-based phase-contrast X-ray tomography
2017 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 25, no 26, p. 33543-33558Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
OPTICAL SOC AMER, 2017
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-224073 (URN)10.1364/OE.25.033543 (DOI)000418893200122 ()2-s2.0-85039066011 (Scopus ID)
Note

QC 20180314

Available from: 2018-03-14 Created: 2018-03-14 Last updated: 2018-09-06Bibliographically approved
Fogelqvist, E., Kördel, M., Carannante, V., Önfelt, B. & Hertz, H. (2017). Laboratory cryo x-ray microscopy for 3D cell imaging. Scientific Reports, 7, Article ID 13433.
Open this publication in new window or tab >>Laboratory cryo x-ray microscopy for 3D cell imaging
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13433Article in journal (Refereed) Published
Abstract [en]

Water-window x-ray microscopy allows two-and three-dimensional (2D and 3D) imaging of intact unstained cells in their cryofixed near-native state with unique contrast and high resolution. Present operational biological water-window microscopes are based at synchrotron facilities, which limits their accessibility and integration with complementary methods. Laboratory-source microscopes have had difficulty addressing relevant biological tasks with proper resolution and contrast due to long exposure times and limited up-time. Here we report on laboratory cryo x-ray microscopy with the exposure time, contrast, and reliability to allow for routine high-spatial resolution 3D imaging of intact cells and cell-cell interactions. Stabilization of the laser-plasma source combined with new optics and sample preparation provide high-resolution cell imaging, both in 2D with ten-second exposures and in 3D with twenty-minute tomography. Examples include monitoring of the distribution of carbon-dense vesicles in starving HEK293T cells and imaging the interaction between natural killer cells and target cells.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-217434 (URN)10.1038/s41598-017-13538-2 (DOI)000413188400014 ()29044158 (PubMedID)2-s2.0-85031924153 (Scopus ID)
Note

QC 20171117

Available from: 2017-11-17 Created: 2017-11-17 Last updated: 2017-11-17Bibliographically approved
Vågberg, W., Larsson, J. C. & Hertz, H. (2017). Removal of ring artifacts in microtomography by characterization of scintillator variations. Optics Express, 25(19), 23191-23198
Open this publication in new window or tab >>Removal of ring artifacts in microtomography by characterization of scintillator variations
2017 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 25, no 19, p. 23191-23198Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
OPTICAL SOC AMER, 2017
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-215825 (URN)10.1364/OE.25.023191 (DOI)000411584600089 ()29041621 (PubMedID)2-s2.0-85029526180 (Scopus ID)
Note

QC 20171017

Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2020-03-09Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2723-6622

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