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Larsson, D. H., Vågberg, W., Yaroshenko, A., Yildirim, A. O. & Hertz, H. (2016). High-resolution short- exposure small-animal laboratory x-ray phase-contrast tomography. Scientific Reports, 6, Article ID 39074.
Open this publication in new window or tab >>High-resolution short- exposure small-animal laboratory x-ray phase-contrast tomography
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 39074Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-199480 (URN)10.1038/srep39074 (DOI)000389631500001 ()2-s2.0-85006105732 (Scopus ID)
Note

QC 20170120

Available from: 2017-01-20 Created: 2017-01-09 Last updated: 2018-09-06Bibliographically approved
Hertz, H. M., Burvall, A., Larsson, D. H., Larsson, J., Lundström, U., Vågberg, W. & Zhou, T. (2016). Propagation-based phase-contrast imaging with laboratory sources. In: Optics InfoBase Conference Papers: . Paper presented at Compact EUV and X-ray Light Sources, EUVXRAY 2016, 20 March 2016 through 22 March 2016. OSA - The Optical Society
Open this publication in new window or tab >>Propagation-based phase-contrast imaging with laboratory sources
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2016 (English)In: Optics InfoBase Conference Papers, OSA - The Optical Society , 2016Conference paper, Published 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. 

Place, publisher, year, edition, pages
OSA - The Optical Society, 2016
Keywords
Biomedical objects, Laboratory source, Micro focus, Phase contrast X-ray imaging, Phase-contrast imaging, State of the art, Very high spatial resolutions, Light sources
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-207507 (URN)2-s2.0-85016454260 (Scopus ID)9781943580095 (ISBN)
Conference
Compact EUV and X-ray Light Sources, EUVXRAY 2016, 20 March 2016 through 22 March 2016
Note

Conference code: 134308; Export Date: 22 May 2017; Conference Paper; Correspondence Address: Hertz, H.M.; Dept. of Applied Physics, Royal Inst. of Technol. (KTH)Sweden; email: hertz@biox.kth.se. QC 20170607

Available from: 2017-06-07 Created: 2017-06-07 Last updated: 2018-02-27Bibliographically approved
Larsson, D. (2015). Small-Animal Imaging with Liquid-Metal-Jet X-Ray Sources. (Doctoral dissertation). Stockholm: KTH Royal Institute of Technology
Open this publication in new window or tab >>Small-Animal Imaging with Liquid-Metal-Jet X-Ray Sources
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Small-animal x-ray imaging is an important tool for medical research. The penetration power of x-rays makes it possible to investigate the 3D structure of small animals and other thick biological samples by computed tomography (CT). However, small-animal x-ray imaging often requires high resolution due to the small structures involved, and short exposure times due to sample movement. This constitutes a challenge, since these two properties require compact x-ray sources with parameters that are not widely available.

In this Thesis we present the first application of liquid-metal-jet sources for small-animal imaging. This source concept was invented at KTH just over ten years ago. The use of a high-speed metal jet as electron-beam target, instead of a solid anode, enables higher x-ray flux while maintaining a small x-ray spot for high-resolution imaging. In the present work, a liquid-metal jet source with a higher-energy spectrum has been developed. It has stronger 24 keV radiation compared to previous sources, which makes it more suitable for imaging of small animals and other few-cm-thick objects, which require the higher penetration of 20-35 keV x-rays.

We have applied the liquid-metal-jet x-ray sources for whole-body imaging of sacrificed mice and zebrafish. With high-resolution absorption-contrast CT we have visualized fine bone details of mice. We have also used phase contrast, a new method that can considerably improve imaging of, e.g., soft tissue, for demarcation of mm-sized tumors inside a full mouse and for mouse cartilage imaging. In zebrafish imaging, we have exploited the greatly enhanced contrast of phase-imaging to resolve single muscle fibers (and possibly even myofibrils) in whole zebrafish in a laboratory setting for the first time. The muscle structures have diameters in the 5-7 μm range and extremely low contrast, which makes them difficult to observe.

With phase contrast, we have demonstrated low-dose and high-resolution angiography of mouse and rat organs and tissues ex vivo. We show detection of blood vessels with diameters below 10 μm with radiation doses compatible with living small animals, which is not possible with absorption contrast and iodinated contrast agents. In addition, we have investigated the vascular network of tumors in mouse ears and visualized the chaotic arrangement of newly-formed blood vessels.

Finally, we present the first results from a new high-power liquid-metal-jet x-ray source prototype, operating at 10× the power of our previous sources, with the same x-ray spot size. This source constitutes an important step towards future in-vivo small-animal laboratory imaging with high resolution.

Abstract [sv]

Röntgenavbildning av små försöksdjur är en viktig metod inom medicinsk forskning. Röntgenstrålar penetrerar material, vilket gör det möjligt att undersöka 3D-strukturen hos försöksdjur och andra tjocka biologiska prov med hjälp av datortomografi (CT). Tyvärr kräver smådjursavbildning ofta dels hög upplösning, eftersom de relevanta strukturerna är små, dels korta exponeringstider, eftersom objektet tenderar att röra sig. Detta är en utmaning, då båda egenskaperna kräver kompakta röntgenkällor med speciella egenskaper som inte är brett tillgängliga.

I denna avhandling visar vi den första användningen av metallstråleröntgenkällor för avbildning av hela smådjur. Den här typen av röntgenkälla uppfanns vid KTH för drygt tio år sedan. Genom att låta elektronerna träffa en stråle av flytande metall, istället för en solid metallanod, kan vi generera mer röntgenstrålning men samtidigt behålla en liten källpunkt, vilket behövs för avbildning med hög upplösning. En ny metallstrålekälla utvecklades som en del av denna avhandling. Den ger ett röntgenspektrum med högre energier, vilket gör källan mer lämpad än tidigare källor för avbildning av små försöksdjur och andra centimetertjocka biologiska objekt.

Vi har använt metallstrålekällor för att avbilda intakta, avlivade möss och zebrafiskar. Med högupplöst absorptions-CT har vi detekterat små bendetaljer inuti möss. Vi har även använt faskontrastavbildning, en ny metod som avsevärt kan förbättra avbildning av mjukvävnad, till att demarkera millimeterstora tumörer inuti en hel mus, samt för avbildning av brosk i leder hos möss. Faskontrast ger en kraftig förstärkning av kontrasten i bilden, vilket även har använts för att för första gången detektera individuella muskelfibrer (och eventuellt även myofibriller) inuti zebrafiskar med en kompakt röntgenkälla. Muskelstrukturerna har diametrar på 5-7 μm och låg kontrast, vilket gör dem svåra att observera.

Med hjälp av faskontrast har vi utvecklat en metod för att avbilda blodkärl med diametrar under 10 μm inuti organ och vävnader från möss och råttor ex vivo, med stråldoser som är kompatibla med studier av levande smådjur. Detta är inte möjligt med konventionell absorptionskontrast och jod-baserade kontrastmedel. Vi har dessutom avbildat nyformade blodkärl kring tumörer i musöron och observerat kärlens kaotiska struktur.

Slutligen presenterar vi de första resultaten från en prototyp av en ny högeffektskälla. Källan har tio gånger högre effekt än tidigare metallstrålekällor, men bibehåller samma storlek på källpunkten. Den här högeffektskällan är ett viktigt steg mot framtida laboratoriebaserad avbildning av levande små försöksdjur med hög upplösning.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. p. ix, 69
Series
TRITA-FYS, ISSN 0280-316X ; 2015:19
Keywords
X-ray, x-ray imaging, small animal, phase contrast, tomography
National Category
Physical Sciences
Research subject
Physics
Identifiers
urn:nbn:se:kth:diva-163169 (URN)978-91-7595-487-5 (ISBN)
Public defence
2015-04-24, Sal FA32, Albanova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20150331

Available from: 2015-03-31 Created: 2015-03-27 Last updated: 2015-04-01Bibliographically approved
Zhou, T., Zanette, I., Zdora, M.-C., Lundström, U., Larsson, D. H., Hertz, H. M., . . . Burvall, A. (2015). Speckle-based x-ray phase-contrast imaging with a laboratory source and the scanning technique. Optics Letters, 40(12), 2822-2825
Open this publication in new window or tab >>Speckle-based x-ray phase-contrast imaging with a laboratory source and the scanning technique
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2015 (English)In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 40, no 12, p. 2822-2825Article in journal (Refereed) Published
Abstract [en]

The speckle-based scanning method for x-ray phase-contrast imaging is implemented with a liquid-metal-jet source. Using the two-dimensional scanning technique, the phase shift introduced by the object is retrieved in both transverse orientations, and the limitations on spatial resolution inherent to the speckle-tracking technique are avoided. This method opens up possibilities of new high-resolution multimodal applications for lab-based phasecontrast x-ray imaging.

Place, publisher, year, edition, pages
Optics Info Base, Optical Society of America, 2015
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-170677 (URN)10.1364/OL.40.002822 (DOI)000356234300038 ()26076271 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council
Note

QC 20150707

Available from: 2015-07-07 Created: 2015-07-03 Last updated: 2017-12-04Bibliographically approved
Zhou, T., Lundström, U., Thüring, T., Rutishauser, S., Larsson, D. H., Stampanoni, M., . . . Burvall, A. (2014). Comparison of propagation-and grating-based x-ray phase-contrast imaging techniques with a liquid-metal-jet source. In: Medical Imaging 2014: Physics of Medical Imaging. Paper presented at Medical Imaging 2014: Physics of Medical Imaging; San Diego, CA; United States; 17 February 2014 through 20 February 2014 (pp. 903353). SPIE - International Society for Optical Engineering
Open this publication in new window or tab >>Comparison of propagation-and grating-based x-ray phase-contrast imaging techniques with a liquid-metal-jet source
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2014 (English)In: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, p. 903353-Conference paper, Published paper (Refereed)
Abstract [en]

X-ray phase-contrast imaging has been developed as an alternative to conventional absorption imaging, partly for its dose advantage over absorption imaging at high resolution. Grating-based imaging (GBI) and propagation-based imaging (PBI) are two phase-contrast techniques used with polychromatic laboratory sources. We compare the two methods by experiments and simulations with respect to required dose. A simulation method based on the projection approximation is designed and verified with experiments. A comparison based on simulations of the doses required for detection of an object with respect to its diameter is presented, showing that for monochromatic radiation, there is a dose advantage for PBI for small features but an advantage for GBI at larger features. However, GBI suffers more from the introduction of polychromatic radiation, in this case so much that PBI gives lower dose for all investigated feature sizes. Furthermore, we present and compare experimental images of biomedical samples. While those support the dose advantage of PBI, they also highlight the GBI advantage of quantitative reconstruction of multimaterial samples. For all experiments a liquid-metal-jet source was used. Liquid-metal-jet sources are a promising option for laboratory-based phase-contrast imaging due to the relatively high brightness and small spot size.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2014
Series
Progress in Biomedical Optics and Imaging, ISSN 1605-7422 ; 9033
Keywords
grating-based, phase-contrast, propagation-based, X-ray imaging
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-146812 (URN)10.1117/12.2043417 (DOI)000338775800173 ()2-s2.0-84901626184 (Scopus ID)978-081949826-7 (ISBN)
Conference
Medical Imaging 2014: Physics of Medical Imaging; San Diego, CA; United States; 17 February 2014 through 20 February 2014
Note

QC 20140616

Available from: 2014-06-16 Created: 2014-06-16 Last updated: 2014-09-08Bibliographically approved
Hertz, H. M., Larsson, J. C., Lundström, U., Larsson, D. H. & Vogt, C. (2014). Laboratory x-ray fluorescence tomography for high-resolution nanoparticle bio-imaging. Optics Letters, 39(9), 2790-2793
Open this publication in new window or tab >>Laboratory x-ray fluorescence tomography for high-resolution nanoparticle bio-imaging
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2014 (English)In: Optics Letters, ISSN 0146-9592, E-ISSN 1539-4794, Vol. 39, no 9, p. 2790-2793Article in journal (Refereed) Published
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.

Keywords
Computerized tomography, Experiments, High energy forming, Mammals, Optical tomography, High brightness, High resolution, Laboratory system, Phantom experiment, Photon counting, Very high spatial resolutions, X ray fluorescence, X-ray fluorescence computed tomography
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-146145 (URN)10.1364/OL.39.002790 (DOI)000335496400067 ()2-s2.0-84899677765 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20140610

Available from: 2014-06-10 Created: 2014-06-09 Last updated: 2018-08-15Bibliographically approved
Lundström, U., Larsson, D. H., Westermark, U. K., Burvall, A. & Hertz, H. M. (2014). Small-Animal microangiography using phase-contrast X-ray imaging and gas as contrast agent. In: Medical Imaging 2014: Physics of Medical Imaging. Paper presented at Medical Imaging 2014: Physics of Medical Imaging; San Diego, CA; United States; 17 February 2014 through 20 February 2014 (pp. 90331L). SPIE - International Society for Optical Engineering
Open this publication in new window or tab >>Small-Animal microangiography using phase-contrast X-ray imaging and gas as contrast agent
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2014 (English)In: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, p. 90331L-Conference paper, Published paper (Refereed)
Abstract [en]

We use propagation-based phase-contrast X-ray imaging with gas as contrast agent To visualize The microvasculature in small animals like mice and rats. The radiation dose required for absorption X-ray imaging is proportional To The minus fourth power of The structure size To be detected. This makes small vessels impossible To image at reasonable radiation doses using The absorption of conventional iodinated contrast agents. Propagation-based phase contrast gives enhanced contrast for high spatial frequencies by moving The detector away from The sample To let phase variations in The Transmitted X-rays develop into intensity variations at The detector. Blood vessels are normally difficult To observe in phase contrast even with iodinated contrast agents as The density difference between blood and most Tissues is relatively small. By injecting gas into The blood stream This density difference can be greatly enhanced giving strong phase contrast. One possible gas To use is carbon dioxide, which is a clinically accepted X-ray contrast agent. The gas is injected into The blood stream of patients To Temporarily displace The blood in a region and Thereby reduce The X-ray absorption in The blood vessels. We have shown That This method can be used To image blood vessels down To 8 μm in diameter in mouse ears. The low dose requirements of This method indicate a potential for live small-Animal imaging and longitudinal studies of angiogenesis.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2014
Series
Progress in Biomedical Optics and Imaging, ISSN 1605-7422 ; 9033
Keywords
X-ray, phase contrast, propagation-based phase contrast, angiography, contrast agent
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-146783 (URN)10.1117/12.2043705 (DOI)000338775800054 ()2-s2.0-84901594060 (Scopus ID)978-081949826-7 (ISBN)
Conference
Medical Imaging 2014: Physics of Medical Imaging; San Diego, CA; United States; 17 February 2014 through 20 February 2014
Note

QC 20140617

Available from: 2014-06-17 Created: 2014-06-16 Last updated: 2014-08-19Bibliographically approved
Zanette, I., Zhou, T., Burvall, A., Lundström, U., Larsson, D. H., Zdora, M., . . . Hertz, H. M. (2014). Speckle-Based X-Ray Phase-Contrast and Dark-Field Imaging with a Laboratory Source. Physical Review Letters, 112(25), 253903
Open this publication in new window or tab >>Speckle-Based X-Ray Phase-Contrast and Dark-Field Imaging with a Laboratory Source
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2014 (English)In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 112, no 25, p. 253903-Article in journal (Refereed) Published
Abstract [en]

We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.

Place, publisher, year, edition, pages
American Physical Society, 2014
Keywords
Scattering, Information, Tomography, Retrieval
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-148281 (URN)10.1103/PhysRevLett.112.253903 (DOI)000338284900009 ()2-s2.0-84903522889 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, StG 240142 279753
Note

QC 20140807

Available from: 2014-08-07 Created: 2014-08-05 Last updated: 2017-12-05Bibliographically approved
Lundström, U., Westermark, U. K., Larsson, D. H., Burvall, A., Arsenian Henriksson, M. & Hertz, H. M. (2014). X-ray phase contrast with injected gas for tumor microangiography. Physics in Medicine and Biology, 59(11), 2801-2811
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, p. 2801-2811Article 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.

Keywords
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
Zhou, T., Lundström, U., Thüring, T., Rutishauser, S., Larsson, D. H., Stampanoni, M., . . . Burvall, A. (2013). Comparison of two x-ray phase-contrast imaging methods with a microfocus source. Optics Express, 21(25), 30183-30195
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, p. 30183-30195Article 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.

Keywords
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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9487-669X

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