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Li, Y., Shaker, K., Larsson, J. C., Vogt, C., Hertz, H. M. & Toprak, M. S. (2018). A Library of Potential Nanoparticle Contrast Agents for X-Ray Fluorescence Tomography Bioimaging. Contrast Media & Molecular Imaging, Article ID UNSP 8174820.
Open this publication in new window or tab >>A Library of Potential Nanoparticle Contrast Agents for X-Ray Fluorescence Tomography Bioimaging
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2018 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, article id UNSP 8174820Article in journal (Refereed) Published
Abstract [en]

Nanoparticles (NPs) have been used as contrast agents for several bioimaging modalities. X-ray fluorescence (XRF) tomography can provide sensitive and quantitative 3D detection of NPs. With spectrally matched NPs as contrast agents, we demonstrated earlier in a laboratory system that XRF tomography could achieve high-spatial-resolution tumor imaging in mice. Here, we present the synthesis, characterization, and evaluation of a library of NPs containing Y, Zr, Nb, Rh, and Ru that have spectrally matched K-shell absorption for the laboratory scale X-ray source. The K-shell emissions of these NPs are spectrally well separated from the X-ray probe and the Compton background, making them suitable for the lab-scale XRF tomography system. Their potential as XRF contrast agents is demonstrated successfully in a small-animal equivalent phantom, confirming the simulation results. The diversity in the NP composition provides a flexible platform for a better design and biological optimization of XRF tomography nanoprobes.

Place, publisher, year, edition, pages
WILEY-HINDAWI, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-242269 (URN)10.1155/2018/8174820 (DOI)000455608200001 ()2-s2.0-85059939967 (Scopus ID)
Note

QC 20190201

Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-08-20Bibliographically 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 ()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: 2018-10-16Bibliographically approved
Larsson, J. C. (2018). Laboratory x-ray fluorescence tomography. (Doctoral dissertation). Stockholm: KTH Royal Institute of Technology
Open this publication in new window or tab >>Laboratory x-ray fluorescence tomography
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

X-ray fluorescence (XRF) tomography is an emerging bio-imaging modality with potential for high-resolution molecular imaging in 3D. 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 XRF tomographysystems 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 (SNR). Other macroscopic biomedical imaging methods provide either structural information with high spatial resolution (e.g., CT) or functional/molecularinformation with lower resolution (e.g., PET).

In this Thesis we present a laboratory XRF tomography system with high spatial resolution (sub-200 μm), low NP concentration and vastly reduced 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 two photon counting detectors. By using the source’s characteristic 24 keV line emission together with spectrally matched molybdenum NPs the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the NPs, as well as the absorption of the object. An iterative method is used to get aquantitative reconstruction of the XRF image. The reconstructed absorption and XRF images are finally combined into a single 3D overlay image.

Using this system we have demonstrated high-resolution dual CT and XRF imaging of both phantoms and mice at radiation doses compatible with in vivo small-animal imaging.

Abstract [sv]

Röntgenfluorescenstomografi (RFT) är en framväxande avbildningsteknik med potential för högupplöst molekylär avbildning i 3D. Den här tekniken mäter fluorescenssignalen från nanopartiklar vilket ger information om både nanopartiklarnas distribution och koncentration inuti objektet. Nuvarande kompakta system har begränsad upplösning (>1 mm), långa mättider och hög stråldos även vid höga koncentrationer av nanopartiklar, främst på grund av låg effektivitet och dåligt signal-brus-förhållande. Andra makroskopiska avbildningsmetoder ger antingen morfologisk information med hög upplösning (e.g., datortomografi) eller funktionell/molekylär information med lägre upplösning (e.g., positronemissionstomografi).

I denna avhandling presenterar vi ett kompakt RFT-system med hög upplösning (200 μm), låg nanopartikelkoncentration och drastiskt reducerade mättider och dos, vilket öppnar upp möjligheter för in vivo-forskning på smådjur. Systemet består av en metallstrålekälla, röntgenoptik och två fotonräknande detektorer. Genom att använda källans karakteristiska emissionslinje vid 24 keV tillsammans med spektralt matchade molybden-nanopartiklar minskar bakgrunden från Comptonspridning drastiskt, vilket ökar signal-brus-förhållandet. Varje mätning ger både information om nanopartiklarnas distribution och koncentration, samt om objektets absorption. En iterativ metod används för att ge en kvantitativ rekonstruktion av röntgenfluorescensbilden. De rekonstruerade röntgenfluorescens- och absorptionsbilderna kombineras slutligen till en enda 3D-bild.

Med det här systemet har vi demonstrerat högupplöst avbildning av både fantomer och möss vid stråldoser som är kompatibla med in vivo-avbildning av smådjur.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2018. p. xi, 67
Series
TRITA-SCI-FOU ; 2018:16
Keywords
x-ray, fluorescence, x-ray fluorescence, nanoparticle, xrf, xfct, tomography
National Category
Physical Sciences
Research subject
Physics
Identifiers
urn:nbn:se:kth:diva-233149 (URN)978-91-7729-796-3 (ISBN)
Public defence
2018-09-07, FR4, Albanova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20180816

Available from: 2018-08-16 Created: 2018-08-15 Last updated: 2018-08-16Bibliographically 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 ()2-s2.0-85029526180 (Scopus ID)
Note

QC 20171017

Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2018-09-06Bibliographically 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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9637-970X

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