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Virtual histology by laboratory x-ray phase-contrast tomography
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0002-6716-1795
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Detailed imaging of biological samples is central to different fields of research, as well as for clinical pathology. Classical histology, using light- orelectron microscopy, can generate high-resolution images but is destructive and only gives two-dimensional information. With virtual histology, athree-dimensional reconstruction of the sample is instead generated, whichcan be virtually sectioned in arbitrary directions. This Thesis presents developments of x-ray phase-contrast computed tomography (CT) as a tool forvirtual histological analysis. In particular, the focus is imaging with laboratory systems as opposed to at large-scale synchrotron facilities, and usingphase-contrast imaging as an alternative to chemical contrast agents.A broad range of imaging applications are demonstrated, from archaeology to clinical pathology, where acquisition and data processing have beenoptimised for each sample. A micro-CT system based on a liquid-metaljet x-ray source was used for imaging centimetre-sized samples. Threedimensional imaging of mummified remains was demonstrated, with sufficient contrast and resolution within the soft tissue to capture microanatomical details; blood vessels, skin layers, fingerprints and remains of adiposecells were visualised in the hand of an ancient Egyptian mummy. Virtualhistology was also performed on paraffin-embedded excised tumours foranalysis of the resection margin, and on rat bones for mapping the vascularcanals.For imaging with micrometre resolution, a nano-CT system was builtand characterised. Photoreceptor imaging in unstained compound eyes ofbumblebees was demonstrated, and light- and electron microscopy wereused to verify the results. Comparisons with conventional attenuationmicro-CT and synchrotron radiation tomography, with both unstained andstained samples, showed the advantage of using phase contrast instead ofstaining the samples

Abstract [sv]

Detaljerad avbildning av biologiska prover är viktigt för olika forskningsområden såväl som för klinisk patologi. Klassisk histologi, genom ljus- ellerelektronmikroskopi, ger högupplösta bilder men är destruktiv och kan endast ge tvådimensionell information. Med virtuell histologi genereras istället en tredimensionell rekonstruktion av provet, vilken kan analyseras genom snittning i godtyckliga riktningar. Den här Avhandlingen presenterarvidareutvecklingar av faskontrast-baserad röntgentomografi (CT), som ettverktyg för virtuell histologi. I synnerhet ligger fokus på avbildning medlabbaserade system, i motsats till storskaliga synkrotronljusanläggningar,och på faskontrastavbildning som ett alternativ till kemiska kontrastmedel.En bredd av olika tillämpningar presenteras, från arkeologi till kliniskpatologi, med datainsamling och databehandling anpassade för varje prov.Ett mikro-CT-system baserat på en metallstråle-röntgenkälla användes föravbildning av centimeterstora prover. Tredimensionell avbildning av mumifierade kvarlevor demonstrerades, med tillräcklig kontrast och upplösning i mjukvävnader för att fånga mikroanatomiska detaljer; blodkärl, hudlager, fingeravtryck och rester av fettceller kunde visualiseras i en egyptiskmumiehand. Virtuell histologi tillämpades också på paraffininbäddade tumörer för analys av resektionsmarginal, och på råttben för avbildning avvaskulära kanaler.För avbildning med mikrometerupplösning byggdes ett nano-CTsystem. Efter karaktärisering av systemet demonstrerades avbildning avfotoreceptorer i ofärgade facettögon från humlor. Ljus- och elektronmikroskopi användes för att verifiera resultaten. Jämförelser med konventionellattenuationsbaserad mikro-CT samt synkrotronljustomografi, både medofärgade och färgade prover, visade på fördelarna med användning avfaskontrast istället för att färga proverna.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2021. , p. 69
Series
TRITA-SCI-FOU ; 2021:07
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Physics, Biological and Biomedical Physics
Identifiers
URN: urn:nbn:se:kth:diva-290960ISBN: 978-91-7873-806-9 (print)OAI: oai:DiVA.org:kth-290960DiVA, id: diva2:1531864
Public defence
2021-03-26, Via zoom https://kth-se.zoom.us/j/66938252095, 13:00 (English)
Opponent
Supervisors
Available from: 2021-03-01 Created: 2021-02-26 Last updated: 2022-06-25Bibliographically approved
List of papers
1. Soft-Tissue Imaging in a Human Mummy: Propagation-based Phase-Contrast CT
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: 2022-12-06Bibliographically approved
2. Imaging fingerprints of an ancient Egyptian mummy by propagation-based phase-contrast x-ray tomography
Open this publication in new window or tab >>Imaging fingerprints of an ancient Egyptian mummy by propagation-based phase-contrast x-ray tomography
2018 (English)In: Proceedings of the 14th International Conference on X-ray Microscopy (XRM2018), 2018Conference paper, Published paper (Refereed)
National Category
Medical Imaging Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:kth:diva-290957 (URN)
Conference
14th International Conference on X-ray Microscopy, Saskatoon, Saskatchewan, Canada, from August 19-24, 2018.
Note

QC 20210301

Available from: 2021-02-26 Created: 2021-02-26 Last updated: 2025-02-09Bibliographically approved
3. Virtual histology of dried and mummified biological samples by laboratory phase-contrast tomography
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 - The International Society for Optics and Photonics, 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 - The International Society for Optics and Photonics, 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)
Conference
X-Ray Nanoimaging: Instruments and Methods IV 2019; San Diego; United States; 11 August 2019 through 12 August 2019
Note

Part of ISBN 9781510629172

QC 20200116

Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2024-03-15Bibliographically approved
4. Laboratory phase-contrast nanotomography of unstained Bombus terrestris compound eyes
Open this publication in new window or tab >>Laboratory phase-contrast nanotomography of unstained Bombus terrestris compound eyes
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-290958 (URN)
Note

QC 20210302

Available from: 2021-02-26 Created: 2021-02-26 Last updated: 2022-06-25Bibliographically approved
5. Laboratory x-ray virtual histology for 3D tumor resection margin assessment
Open this publication in new window or tab >>Laboratory x-ray virtual histology for 3D tumor resection margin assessment
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-290959 (URN)
Note

QC 20210302

Available from: 2021-02-26 Created: 2021-02-26 Last updated: 2022-06-25Bibliographically approved
6. Cellular-Resolution Imaging of Microstructures in Rat Bone using Laboratory Propagation-Based Phase-Contrast X-ray Tomography
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
Show others...
2018 (English)In: Microscopy and Microanalysis, 2018, Vol. 24, p. 368-369Conference paper, Published paper (Refereed)
National Category
Medical Imaging 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: 2025-02-09Bibliographically approved

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  • nn-NO
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