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Phase-Contrast X-Ray Carbon Dioxide Angiography
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. (Biomedical and x-ray physics)ORCID iD: 0000-0001-7637-1850
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Phase-contrast x-ray imaging is an emerging technology, which allows for imaging of smaller features than conventional absorption-based x-ray imaging, with lower radiation dose. Instead of the attenuation that is normally used in x-ray imaging, it utilizes the phase shift introduced by an object to the transmitted x-rays. This phase shift can change the directions of the x-rays slightly, which can be measured in a few different ways. Propagation-based phase contrast, which is the method most used in this Thesis, detects these deviations using a high-resolution imaging detector at a distance from the sample. This Thesis describes how phase-contrast x-ray imaging can be used to image the internal structures of small animals like mice and rats. A technique for imaging of very small blood vessels has been developed and analyzed. By injecting a gas, such as carbon dioxide, into the vascular system, blood vessels down to 8 µm in diameter have been visualized. This is considerably smaller than the 50 µm vessels that can be imaged using iodine-based contrast agents at radiation doses compatible with living animals. A recently invented type of x-ray source, based on a jet of liquid metal as electron-beam target, has been used and further developed for the imaging purposes of this Thesis. Such metal-jet x-ray sources provide very high x-ray flux for the small x-ray spot sizes at which they operate, something that has been crucial for the quality of the phase-contrast images acquired.

Abstract [sv]

Faskontrastavbildning med röntgenstrålning är en relativt ny teknik som gör det möjligt att avbilda mindre detaljer än vanlig absorptionsbaserad röntgen, med lägre stråldos. Där normalt dämpningen av strålningen registreras, används istället det fasskift som strålningen får då den går genom ett objekt. Detta fasskift kan få röntgenstrålarna att ändra riktning, vilket kan mätas på olika sätt. Propagationsbaserad faskontrast, som har använts mest i denna avhandling, detekterar avvikelserna i fasen med hjälp av en röntgenkamera med hög upplösning en bit bakom objektet. Denna avhandling beskriver hur faskontrast kan användas för att avbilda inre strukturer i små djur som möss och råttor. En teknik för avbildning av mycket små blodkärl har utvecklats och analyserats. Genom att injicera en gas, såsom koldioxid, in i kärlsystemet har blodkärl ner till 8 µm i diameter visualiserats. Detta är betydligt mindre än de 50 µm-kärl som kan avbildas med jodbaserade kontrastmedel vid stråldoser som går att använda på levande försöksdjur. En nyligen uppfunnen typ av röntgenkälla, som skjuter elektroner på en stråle av flytande metall, har använts och utvecklats för avbildningen i denna avhandling. Dessa metallstrålekällor ger mycket röntgenstrålning för den lilla källpunkt de har, något som varit avgörande för kvaliteten på faskontrastbilderna i denna avhandling.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2014. , ix, 66 p.
Series
TRITA-FYS, ISSN 0280-316X ; 2013:70
National Category
Physical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-139409ISBN: 978-91-7501-971-0 (print)OAI: oai:DiVA.org:kth-139409DiVA: diva2:687022
Public defence
2014-01-31, FD5, AlbaNova universitetscentrum, Roslagstullsbacken 21, Stockholm, 13:00 (English)
Opponent
Supervisors
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research
Note

QC 20140113

Available from: 2014-01-14 Created: 2014-01-13 Last updated: 2014-01-14Bibliographically approved
List of papers
1. Phase retrieval in X-ray phase-contrast imaging suitable for tomography
Open this publication in new window or tab >>Phase retrieval in X-ray phase-contrast imaging suitable for tomography
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2011 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 19, no 11, 10359-10376 p.Article in journal (Refereed) Published
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.

National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:kth:diva-34364 (URN)10.1364/OE.19.010359 (DOI)000290852800033 ()21643293 (PubMedID)2-s2.0-79957611071 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20110705

Available from: 2011-07-05 Created: 2011-06-07 Last updated: 2017-12-11Bibliographically approved
2. A 24 keV liquid-metal-jet x-ray source for biomedical applications
Open this publication in new window or tab >>A 24 keV liquid-metal-jet x-ray source for biomedical applications
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2011 (English)In: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 82, no 12, 123701- p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Institute of Physics (AIP), 2011
Keyword
x-ray imaging, x-ray source, phase contrast
National Category
Medical Equipment Engineering
Identifiers
urn:nbn:se:kth:diva-62137 (URN)10.1063/1.3664870 (DOI)000298643100029 ()22225218 (PubMedID)2-s2.0-84855323212 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20120118

Available from: 2012-01-18 Created: 2012-01-18 Last updated: 2017-12-08Bibliographically approved
3. X-ray phase contrast for CO2 microangiography
Open this publication in new window or tab >>X-ray phase contrast for CO2 microangiography
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2012 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 9, 2603-2617 p.Article in journal (Refereed) Published
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.

Keyword
Angiography, Blood vessels, Carbon dioxide, Dosimetry, Image quality, Imaging techniques, Visualization, X ray apparatus, X rays
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-95082 (URN)10.1088/0031-9155/57/9/2603 (DOI)000303046200015 ()22505599 (PubMedID)2-s2.0-84860168376 (Scopus ID)
Funder
Swedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20120522

Available from: 2012-05-22 Created: 2012-05-14 Last updated: 2017-12-07Bibliographically approved
4. X-ray phase-contrast CO2 angiography for sub-10 mu m vessel imaging
Open this publication in new window or tab >>X-ray phase-contrast CO2 angiography for sub-10 mu m vessel imaging
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2012 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 22, 7431-7441 p.Article in journal (Refereed) Published
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.

Keyword
Future-Prospects, Angiogenesis, Retrieval, Agents
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-109639 (URN)10.1088/0031-9155/57/22/7431 (DOI)000310838700017 ()2-s2.0-84869037603 (Scopus ID)
Funder
Swedish Research Council, VR 2009-3142Knut and Alice Wallenberg Foundation, KAW 2011.0136
Note

QC 20130109

Available from: 2013-01-09 Created: 2013-01-08 Last updated: 2017-12-06Bibliographically approved
5. First application of liquid-metal-jet sources for small-animal imaging: High-resolution CT and phase-contrast tumor demarcation
Open this publication in new window or tab >>First application of liquid-metal-jet sources for small-animal imaging: High-resolution CT and phase-contrast tumor demarcation
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2013 (English)In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 2, 021909- p.Article in journal (Refereed) Published
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.

Keyword
small-animal imaging, liquid-metal-jet, x-ray, CT, tumor demarcation, mouse
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-119468 (URN)10.1118/1.4788661 (DOI)000314727700038 ()23387757 (PubMedID)2-s2.0-84873576570 (Scopus ID)
Funder
Swedish Research CouncilVinnova
Note

QC 20130319

Available from: 2013-03-19 Created: 2013-03-14 Last updated: 2017-12-06Bibliographically approved
6. X-ray grating interferometry with a liquid-metal-jet source
Open this publication in new window or tab >>X-ray grating interferometry with a liquid-metal-jet source
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2013 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 103, no 9, 091105- p.Article in journal (Refereed) Published
Abstract [en]

A liquid-metal-jet X-ray tube is used in an X-ray phase-contrast microscope based on a Talbot type grating interferometer. With a focal spot size in the range of a few microns and a photon flux of similar to 10(12) photons/s x sr, the brightness of such a source is approximately one order of magnitude higher than for a conventional microfocus source. For comparison, a standard microfocus source was used with the same grating interferometer, showing significantly increased visibility for the liquid-metal-jet arrangement. Together with the increased flux, this results in improved signal-to-noise ratio.

Place, publisher, year, edition, pages
American Institute of Physics (AIP), 2013
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-129628 (URN)10.1063/1.4819766 (DOI)000323846900005 ()2-s2.0-84884176871 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20131003

Available from: 2013-10-03 Created: 2013-10-03 Last updated: 2017-12-06Bibliographically approved
7. Comparison of two x-ray phase-contrast imaging methods with a microfocus source
Open this publication in new window or tab >>Comparison of two x-ray phase-contrast imaging methods with a microfocus source
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2013 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 21, no 25, 30183-30195 p.Article in journal (Refereed) Published
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.

Keyword
Computed-Tomography, Grating Interferometer, Noise, Propagation, Performance, Retrieval, Signal, Jet, CT
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-139423 (URN)10.1364/OE.21.030183 (DOI)000328575700007 ()2-s2.0-84890505484 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20140113

Available from: 2014-01-13 Created: 2014-01-13 Last updated: 2017-12-06Bibliographically approved
8. X-ray phase contrast with injected gas for tumor microangiography
Open this publication in new window or tab >>X-ray phase contrast with injected gas for tumor microangiography
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2014 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 11, 2801-2811 p.Article in journal (Refereed) Published
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.

Keyword
x-ray, phase-contrast, angiography, tumor, propagation-based, microangiography, gas
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-139504 (URN)10.1088/0031-9155/59/11/2801 (DOI)000336459000016 ()2-s2.0-84900469948 (Scopus ID)
Funder
Swedish Research CouncilSwedish Cancer Society
Note

QC 20140624. Updated from manuscript to article in journal.

Available from: 2014-01-14 Created: 2014-01-14 Last updated: 2017-12-06Bibliographically approved

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