Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 26;25(9):4733.
doi: 10.3390/ijms25094733.

High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study

Kunal Kumar  1 , Melanie Fachet  1 , Christoph Hoeschen  1
Affiliations

High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study

Kunal Kumar et al. Int J Mol Sci. .

Abstract

X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still limited to lighter elements (i.e., atomic number Z≤45). This study investigates the feasibility of focusing hard X-rays from solid-target tubes using ellipsoidal lens systems composed of mosaic graphite crystals with the aim of enabling high-resolution in vivo XFI applications with mid-Z (42≤Z≤64) elements. Monte Carlo simulations are performed to characterize the proposed focusing-optics concept and provide quantitative predictions of the XFI sensitivity, in silico tumor-bearing mice models loaded with palladium (Pd) and barium (Ba) NPs. Based on simulation results, the minimum detectable total mass of PdNPs per scan position is expected to be on the order of a few hundred nanograms under in vivo conform conditions. PdNP masses as low as 150 ng to 50 ng could be detectable with a resolution of 600 μm when imaging abdominal tumor lesions across a range of low-dose (0.8 μGy) to high-dose (8 μGy) exposure scenarios. The proposed focusing-optics concept presents a potential step toward realizing XFI with conventional X-ray tubes for high-resolution applications involving interesting NP formulations.

Keywords: Geant4; HOPG/HAPG optics; X-ray fluorescence imaging; nanoparticles.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Spatial properties of the proposed ellipsoidal optics. (a) The dependence of the projection (blue) and cross-sectional (green) FWHM of the focused beam on the size (FWHM) of the X-ray source spot. (b) Normalized intensity distribution on the focal plane for source size of 320 μm FWHM and m=0.12°. The red and cyan solid/dotted lines represent the focused beam’s horizontal and vertical projection/cross-section FWHM.
Figure 2
Figure 2
Rocking curve and spectral characterization of the Bragg-reflecting GrO. (a) Rocking curve evaluation on planar GrO considering a source size of 320 μm FWHM and 59 keV monochromatic beams. (b) Comparison of the photon flux density in units of photons per mm2 and at f=320 mm between the direct X-rays (blue) and the focused X-rays using ellipsoidal GrO.
Figure 3
Figure 3
Comparison of significance (Z, see Equation (9)) at low-dose mode XFI across varying tumor lesion (target sphere) sizes within the subcutaneous, liver, and kidney regions. (a) A typical simulated XRF spectrum per scan position corresponding to the voxelized 3D mouse model and featuring palladium (Pd) and barium (Ba) as contrast agents within the target spheres. Significance (mean values ± standard deviation) of (b) Pd-Kα and (c) Ba-Kα fluorescence at varying agent concentrations within tumor lesions of 0.5 mm, 1.25 mm, and 5 mm diameter positioned inside the three organ regions. The black dashed line indicates a significance (Z) cutoff of Z=5, and the magenta dotted line indicates Z=3. Significance (mean values and standard deviation in brackets) of Pd-Kα fluorescence for varying agent concentrations and target sizes within the (d) subcutaneous, (e) liver, and (f) kidney regions.
Figure 4
Figure 4
Fluorescence imaging of palladium (Pd-Kα) and barium (Ba-Kα) contrast agents at high-dose mode with SDDs. (a) A typical simulated XRF spectrum per scan position. Significance (mean values ± standard deviation) of (b) Pd-Kα and (c) Ba-Kα fluorescence at varying agent concentrations within tumor lesions (1 mm and 5 mm diameter) positioned inside three organ regions.
Figure 5
Figure 5
Fluorescence imaging of barium (Ba-Kα) contrast agents at low-dose mode with CdTe detectors. (a) A typical simulated XRF spectrum per scan position. (b) Comparison of Ba-Kα significance (mean values ± standard deviation) for varying agent concentrations and tumor sizes (0.5 mm, 1.25 mm, and 5 mm diameter) within the subcutaneous, liver, and kidney regions.
Figure 6
Figure 6
Fluorescence imaging of barium (Ba-Kα) contrast agents at high-dose mode with CdTe detectors. (a) A typical simulated XRF spectrum per scan position. (b) Significance (mean values ± standard deviation) of Ba-Kα fluorescence at varying agent concentrations within tumor lesions (1 mm and 5 mm diameter) positioned inside three organ regions.
Figure 7
Figure 7
Comparison of organ doses across low-dose and high-dose mode fluorescence imaging. (a) Organ doses in the low-dose mode and (b) in the high-dose mode are shown for the three organ scan positions that include the tumor target, i.e., (blue) subcutaneous, (orange) liver, and (golden) kidney region. Herein, the tumor dose corresponds to a lesion size of 1 mm in diameter.
Figure 8
Figure 8
(a) Illustration depicting photon tracking and interactions with the ellipsoidal GrO setup in Geant4. A total of 104 simulated photon histories are shown, and Bragg-reflected photons can be seen converging downstream of the optics setup. Trajectories of other scattered events can also be seen. (b) A simplified illustration of the optical setup. (c) Schematic diagram (not to scale) showing a cross-sectional view of the optics setup. All units are in mm.
Figure 9
Figure 9
(a) An exemplary image of the simulation setup. The red arrow (see the inset image) highlights the tumor lesion (golden sphere) embedded within the mouse liver. (b) Volume rendering of the whole-body voxelized mouse model (Digimouse [59,60]) used for the MC simulations.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. James M.L., Gambhir S.S. A molecular imaging primer: Modalities, imaging agents, and applications. Physiol. Rev. 2012;92:897–965. doi: 10.1152/physrev.00049.2010. - DOI - PubMed
    1. Lauber D.T., Fülöp A., Kovács T., Szigeti K., Máthé D., Szijártó A. State of the art in vivo imaging techniques for laboratory animals. Lab. Anim. 2017;51:465–478. doi: 10.1177/0023677217695852. - DOI - PubMed
    1. Carragher N.O., Brunton V.G., Frame M.C. Combining imaging and pathway profiling: An alternative approach to cancer drug discovery. Drug Discov. Today. 2012;17:203–214. doi: 10.1016/j.drudis.2012.02.002. - DOI - PubMed
    1. Levenson R.M., Lynch D.T., Kobayashi H., Backer J.M., Backer M.V. Multiplexing with multispectral imaging: From mice to microscopy. ILAR J. 2008;49:78–88. doi: 10.1093/ilar.49.1.78. - DOI - PubMed
    1. Beckmann N., Kneuer R., Gremlich H.U., Karmouty-Quintana H., Blé F.X., Müller M. In vivo mouse imaging and spectroscopy in drug discovery. NMR Biomed. Int. J. Devoted Dev. Appl. Magn. Reson. In Vivo. 2007;20:154–185. doi: 10.1002/nbm.1153. - DOI - PubMed

Grants and funding

This research received no external funding.

LinkOut - more resources