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Laboratory x-ray fluorescence tomography
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0002-9637-970X
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 [en]
x-ray, fluorescence, x-ray fluorescence, nanoparticle, xrf, xfct, tomography
National Category
Physical Sciences
Research subject
Physics
Identifiers
URN: urn:nbn:se:kth:diva-233149ISBN: 978-91-7729-796-3 (print)OAI: oai:DiVA.org:kth-233149DiVA, id: diva2:1239174
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
List of papers
1. Laboratory x-ray fluorescence tomography for high-resolution nanoparticle bio-imaging
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
2. High-spatial-resolution nanoparticle X-ray fluorescence tomography
Open this publication in new window or tab >>High-spatial-resolution nanoparticle X-ray fluorescence tomography
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2016 (English)In: MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING, 2016, article id 97831VConference paper, Published paper (Refereed)
Abstract [en]

X-ray fluorescence tomography (XFCT) has potential for high-resolution 3D molecular x-ray bio-imaging. 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 XFCT systems 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. We have developed a laboratory XFCT system with high spatial resolution (sub-100 mu m), low NP concentration and vastly decreased 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 an energy-resolving photon-counting detector. By using the source's characteristic 24 keV line-emission together with carefully matched molybdenum nanoparticles the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the Mo nanoparticles. A filtered back-projection method is used to produce the final XFCT image.

Series
Proceedings of SPIE, ISSN 0277-786X ; 9783
Keywords
XFCT, XRF, nanoparticles, molybdenum, fluorescence, x-ray imaging, tomography, molecular imaging
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-189836 (URN)10.1117/12.2216770 (DOI)000378352900064 ()2-s2.0-84978795862 (Scopus ID)978-1-5106-0018-8 (ISBN)
Conference
Conference on Medical Imaging - Physics of Medical Imaging, FEB 28-MAR 02, 2016, San Diego, CA
Note

QC 20160718

Available from: 2016-07-18 Created: 2016-07-15 Last updated: 2018-08-15Bibliographically approved
3. High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles
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
4. Focused anti-scatter grid for background reduction in x-ray fluorescence tomography
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
5. Characterization of scintillator-based detectors for few-ten-keV high-spatial-resolution x-ray imaging
Open this publication in new window or tab >>Characterization of scintillator-based detectors for few-ten-keV high-spatial-resolution x-ray imaging
2016 (English)In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 43, no 6Article in journal (Refereed) Published
Abstract [en]

Purpose: High-spatial-resolution x-ray imaging in the few-ten-keV range is becoming increasingly important in several applications, such as small-animal imaging and phase-contrast imaging. The detector properties critically influence the quality of such imaging. Here the authors present a quantitative comparison of scintillator-based detectors for this energy range and at high spatial frequencies. Methods: The authors determine the modulation transfer function, noise power spectrum (NPS), and detective quantum efficiency for Gadox, needle CsI, and structured CsI scintillators of different thicknesses and at different photon energies. An extended analysis of the NPS allows for direct measurements of the scintillator effective absorption efficiency and effective light yield as well as providing an alternative method to assess the underlying factors behind the detector properties. Results: There is a substantial difference in performance between the scintillators depending on the imaging task but in general, the CsI based scintillators perform better than the Gadox scintillators. At low energies (16 keV), a thin needle CsI scintillator has the best performance at all frequencies. At higher energies (28-38 keV), the thicker needle CsI scintillators and the structured CsI scintillator all have very good performance. The needle CsI scintillators have higher absorption efficiencies but the structured CsI scintillator has higher resolution. Conclusions: The choice of scintillator is greatly dependent on the imaging task. The presented comparison and methodology will assist the imaging scientist in optimizing their high-resolution few-ten-keV imaging system for best performance.

Place, publisher, year, edition, pages
WILEY, 2016
Keywords
X-ray detector, scintillator, MTF, NPS, DQE
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-208598 (URN)10.1118/1.4948687 (DOI)000401300500006 ()27277020 (PubMedID)2-s2.0-84969523666 (Scopus ID)
Funder
Swedish Research Council
Note

QC 20170609

Available from: 2017-06-09 Created: 2017-06-09 Last updated: 2018-08-15Bibliographically approved
6. Removal of ring artifacts in microtomography by characterization of scintillator variations
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

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