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There is a rising awareness of the toxicity of micro- and nanoplastics (MNPs); however, fundamental precise information on MNP-biodistribution in organisms is currently not available. X-ray fluorescence imaging (XFI) is introduced as a promising imaging modality to elucidate the effective MNP bioavailability and is expected to enable exact measurements on the uptake over the physical barriers of the organism and bioaccumulation in different organs. This is possible because of the ability of XFI to perform quantitative studies with a high spatial resolution and the possibility to conduct longitudinal studies. The focus of this work is a numerical study on the detection limits for a selected XFI-marker, here, palladium, to facilitate the design of future preclinical in vivo studies. Based on Monte Carlo simulations using a 3D voxel mouse model, the palladium detection thresholds in different organs under in vivo conditions in a mouse are estimated. The minimal Pd-mass in the scanning position at a reasonable significance level is determined to be <20 ng/mm2 for abdominal organs and <16 μg/mm2 for the brain. MNPs labelled with Pd and homogeneously distributed in the organ would be detectable down to a concentration of <1 μg/mL to <2.5 mg/mL in vivo. Long-term studies with a chronic MNP exposure in low concentrations are therefore possible such that XFI measurements could, in the future, contribute to MNP health risk assessment in small animals and humans. [ABSTRACT FROM AUTHOR]

Bioluminescence imaging (BLI) is a widely used technique in preclinical scientific research, particularly in the development of mRNA-based medications and non-invasive tumor diagnostics. It has become an essential tool in current science. However, the current state of bioluminescence imaging is primarily qualitative, making it challenging to obtain quantitative measurements and to draw accurate conclusions. This fact is caused by the unique properties of optical photons and tissue interactions. In this paper, we propose an experimental setup and Geant4-simulations to gain a better understanding of the optical properties and processes involved in bioluminescence imaging. Our goal is to advance the field towards more quantitative measurements. We will discuss the details of our experimental setup, the data we collected, the outcomes of the Geant4-simulations, and additional information on the underlying physical processes. [ABSTRACT FROM AUTHOR]

Over the full range of all 100 cells, a mean value of 77.03 ± 21.48 fg iodine/cell ( 2.6 × 10 SP -4 sp ± 0.73 ng Q SB 10 sb /cell) was calculated, with a median value of 49.13 fg iodine/cell ( 1.66 × 10 SP -4 sp ng Q SB 10 sb /cell). Control measurements using free iodine, experiments of I SB 2 sb -Q SB 10 sb bioavailability via LC-MS/MS as well as the scans around the cell pellets clearly indicate that the measured iodine masses can only be related to the I SB 2 sb -Q SB 10 sb . (a) 26.7 ng total iodine mass in cell pellet from donor 1, (b) 28.8 ng total iodine mass in cell pellet from donor 2, (c) 27.4 ng total iodine mass in cell pellet from donor 3, (d) no iodine signal in untreated cell sample. The total reconstructed iodine masses in the capillaries were 26.7 ± 4.0 ng, 28.8 ± 4.3 ng and 27.4 ± 4.1 ng for donor 1 (600,000 cells), 2 (600,000 cells) and 3 (400,000 cells), respectively, whereas no iodine could be detected in the untreated cell sample (750,000 cells). [Extracted from the article]

Trace elements, functionalized nanoparticles and labeled entities can be localized with sub-mm spatial resolution by X-ray fluorescence imaging (XFI). Here, small animals are raster scanned with a pencil-like synchrotron beam of high energy and low divergence and the X-ray fluorescence is recorded with an energy-dispersive detector. The ability to first perform coarse scans to identify regions of interest, followed by a close-up with a sub-mm X-ray beam is desirable, because overall measurement time and X-ray dose absorbed by the (biological) specimen can thus be minimized. However, the size of X-ray beams at synchrotron beamlines is usually strongly dependent on the actual beamline setup and can only be adapted within specific pre-defined limits. Especially, large synchrotron beams are non-trivial to generate. Here, we present the concept of graphite-based, convex reflection optics for the one-dimensional enlargement of a 1 mm wide synchrotron beam by a factor of 5 to 10 within a 1 m distance. Four different optics are tested and characterized and their reflection properties compared to ray tracing simulations. The general shape and size of the measured reflection profiles agree with expectations. Enhancements with respect to homogeneity and efficiency can be expected with improved optics manufacturing. A mouse phantom is used for a proof-of-principle XFI experiment demonstrating the applicability of coarse and fine scans with the suggested optics design. [ABSTRACT FROM AUTHOR]

Simple Summary: One novel approach in cancer therapy is the use of genetically modified immune cells that are more specifically directed to a tumor than common chemotherapy. This creates the need for medical imaging methods that can be used to track these immune cells during therapy. Our study provides computer simulations of potential applications of X-ray fluorescence imaging for this purpose. We showed that if immune cells were labeled with gold nanoparticles as an imaging marker, the amounts of immune cells that would be expected to be found in a tumor or inflammation site could be detected with our setup. Our feasibility study thus shows results that are promising estimates on what can be achieved. The growing field of cellular therapies in regenerative medicine and oncology calls for more refined diagnostic tools that are able to investigate and monitor the function and success of said therapies. X-ray Fluorescence Imaging (XFI) can be applied for molecular imaging with nanoparticles, such as gold nanoparticles (GNPs), which can be used in immune cell tracking. We present a Monte Carlo simulation study on the sensitivity of detection and associated radiation dose estimations in an idealized setup of XFI in human-sized objects. Our findings demonstrate the practicability of XFI in human-sized objects, as immune cell tracking with a minimum detection limit of 4.4 × 105 cells or 0.86 μg gold in a cubic volume of 1.78 mm3 can be achieved. Therefore, our results show that the current technological developments form a good basis for high sensitivity XFI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time. [ABSTRACT FROM AUTHOR]