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High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0002-9637-970X
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics.ORCID iD: 0000-0001-5678-5298
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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. Vol. 63, p. 164001-
Keywords [en]
x-ray, x-ray fluorescence, tomography, nanoparticles
National Category
Physical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-233331DOI: 10.1088/1361-6560/aad51eISI: 000441712300001Scopus ID: 2-s2.0-85052501337OAI: oai:DiVA.org:kth-233331DiVA, id: diva2:1239135
Funder
Swedish Research CouncilWallenberg Foundations
Note

QC 20180828

Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2018-10-16Bibliographically approved
In thesis
1. Laboratory x-ray fluorescence tomography
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

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