High-sensitivity imaging and quantification of intratumoral distributions of gold nanoparticles using a benchtop x-ray fluorescence imaging system

Manohar, Nivedh; Reynoso, Francisco J.; Jayarathna, Sandun; Moktan, Hem; Ahmed, Md. Foiez; Diagaradjane, Parmeswaran; Krishnan, Sunil; Cho, Sang Hyun

doi:10.1364/ol.44.005314

Cited by 11 publications

(6 citation statements)

References 16 publications

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“…However, as such a setup that can provide a sufficient flux and narrow energy spectrum is not yet available, those methods currently suffer from the same limitations of long measurement times and a higher dose as presented in our approach. Nevertheless, great sensitivity has been achieved, even reaching synchrotron-like detection thresholds of 0.007 mg Au/mL; however, for ex vivo imaging of small targets [60], whereby using high radiation dose not suited for in vivo imaging. These drawbacks could be vastly improved in a study by Larsson et al [39], pointing out the advantages of a pencil beam driven approach and indicating clinical applicability for molecular imaging in the sub-millimeter range for small targets.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging—A Numerical Study

Kahl

Staufer

Körnig

et al. 2021

IJMS

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Immunotherapy has been a breakthrough in cancer treatment, yet only a subgroup of patients responds to these novel drugs. Parameters such as cytotoxic T-cell infiltration into the tumor have been proposed for the early evaluation and prediction of therapeutic response, demanded for non-invasive, sensitive and longitudinal imaging. We have evaluated the feasibility of X-ray fluorescence imaging (XFI) to track immune cells and thus monitor the immune response. For that, we have performed Monte Carlo simulations using a mouse voxel model. Spherical targets, enriched with gold or palladium fluorescence agents, were positioned within the model and imaged using a monochromatic photon beam of 53 or 85 keV. Based on our simulation results, XFI may detect as few as 730 to 2400 T cells labelled with 195 pg gold each when imaging subcutaneous tumors in mice, with a spatial resolution of 1 mm. However, the detection threshold is influenced by the depth of the tumor as surrounding tissue increases scattering and absorption, especially when utilizing palladium imaging agents with low-energy characteristic fluorescence photons. Further evaluation and conduction of in vivo animal experiments will be required to validate and advance these promising results.

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Section: Discussionmentioning

confidence: 99%

Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging—A Numerical Study

Kahl

Staufer

Körnig

et al. 2021

IJMS

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“…is the mean pixel value of the center of the phantom (a background region where no GNP-induced XRF can be generated); are the associated square of the standard deviations. As in our pervious study [24] and based on the Rose criterion [25], the cutoff threshold value of 3 was selected for the CNR. For values <3, GNPs were considered undetectable.…”

Section: H Contrast-to-noise Ratio In Reconstructed Imagesmentioning

confidence: 99%

Use of the Fully Spectroscopic Pixelated Cadmium Telluride Detector for Benchtop X-Ray Fluorescence Computed Tomography

2022

Self Cite

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In this work, we integrated a commercially-available fully-spectroscopic pixelated cadmium telluride (CdTe) detector system as a two-dimensional (2D) array detector into our existing benchtop conebeam x-ray fluorescence computed tomography (XFCT) system. After integrating this detector, known as High-Energy X-ray Imaging Technology (HEXITEC), we performed quantitative imaging of gold nanoparticle (GNP) distribution in a small animal-sized phantom using our benchtop XFCT system. Owing to the upgraded detector component within our benchtop XFCT system, we were able to conduct this phantom imaging in an unprecedented manner by volumetric XFCT scans followed by XFCT image reconstruction in 3D. The current results showed that adoption of HEXITEC, in conjunction with a custommade parallel-hole collimator, drastically reduced the XFCT scan time/dose. Compared with the previous work performed with our original benchtop XFCT system adopting a single crystal CdTe detector, the currently observed reduction was up to a factor of 5, while achieving comparable GNP detection limit under similar experimental conditions. Overall, we demonstrated, for the first time to the best our knowledge, the feasibility of benchtop XFCT imaging of small animal-sized objects containing biologically relevant GNP concentrations (on the order of 0.1 mg Au/cm 3 or 100 parts-per-million/ppm), with the scan time (on the order of 1 minute)/x-ray dose (on the order of 10 cGy) that are likely meeting the minimum requirements for routine preclinical imaging applications.

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“…As we keep the x-ray collimation angle fixed (AE0.5 mrad), electrons at γ > γ t will emit more photons into the cone, also with a larger bandwidth contribution [Eq. (6)]. The opposite holds for γ < γ t .…”

Section: Appendix B: Electron Bunch Propagation and Energy Spreadmentioning

confidence: 99%

“…Synchrotron radiation (SR) sources have the potential to deliver hard x-rays with high photon number and low bandwidth within a small divergence angle. This makes them an important research tool in many disciplines, including medical research where they could enable novel imaging modalities, such as x-ray fluorescence imaging (XFI) [1][2][3][4][5][6]. Being a scanning imaging modality, XFI explicitly requires pencil-beam geometries, as the spatial resolution is determined by the x-ray beam size.…”

Section: Introductionmentioning

confidence: 99%

Design study for a compact laser-driven source for medical x-ray fluorescence imaging

Brümmer

Debus

Pausch

et al. 2020

Phys. Rev. Accel. Beams

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Thomson scattering sources with their hard x-ray pencil beams represent a promising candidate to drive high-resolution X-ray Fluorescence Imaging (XFI). As XFI is a scanning imaging modality, it specifically requires pencil-beam geometries along with a high beam mobility. In combination with laser-wakefield acceleration (LWFA) such sources could provide the compactness needed for a future transition into clinical application. A sufficient flux within a small bandwidth could enable in-vivo high-sensitivity XFI for early cancer diagnostics and pharmacokinetic imaging. We thus report on a specific all-laser driven source design directed at increasing the photon number within the bandwidth and opening angle defined by XFI conditions. Typical parameters of driver lasers and electron bunches from LWFA are utilized and controlled within realistic parameter regions on the basis of appropriate beam optics. An active plasma lens is implemented for chromatic focal control of the bunch. Source performance limits are identified and compared to existing x-ray sources with regard to their potential to be implemented in future clinical XFI.

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High-sensitivity imaging and quantification of intratumoral distributions of gold nanoparticles using a benchtop x-ray fluorescence imaging system

Cited by 11 publications

References 16 publications

Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging—A Numerical Study

Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging—A Numerical Study

Use of the Fully Spectroscopic Pixelated Cadmium Telluride Detector for Benchtop X-Ray Fluorescence Computed Tomography

Design study for a compact laser-driven source for medical x-ray fluorescence imaging

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