Abstract
X-ray fluorescence imaging (XFI) is a non-invasive detection method of small quantities of elements, which can be excited to emit fluorescence x-ray photons upon irradiation with an incident x-ray beam. In particular, it can be used to measure nanoparticle uptake in cells and tissue, thus making it a versatile medical imaging modality. However, due to substantially increased multiple Compton scattering background in the measured x-ray spectra, its sensitivity severely decreases for thicker objects, so far limiting its applicability for tracking very small quantities under in-vivo conditions. Reducing the detection limit would enable the ability to track labeled cells, promising new insights into immune response and pharmacokinetics. We present a synchrotron-based approach for reducing the minimal detectable marker concentration by demonstrating the feasibility of XFI for measuring the yet inaccessible distribution of the endogenous iodine in murine thyroids under in-vivo conform conditions. This result can be used as a reference case for the design of future preclinical XFI applications as mentioned above.
Highlights
X-ray fluorescence imaging (XFI) is a non-invasive detection method of small quantities of elements, which can be excited to emit fluorescence x-ray photons upon irradiation with an incident x-ray beam
Previous studies based on single photon emission computed tomography (SPECT) and scintigraphy rely on the use of radiotracers—typically between 10 and 300 μCi (0.4 to 11 MBq) 125I or 131I20–24 or even exceeding 800 μCi (30 MBq)[25] and have only been able to detect uptake rates of iodine r adiotracer[26,27]
In the present work we have demonstrated an important milestone towards in-vivo XFI—the spatially resolved quantitative measurement of the endogenous iodine mass in murine thyroids, introducing a benchmark for the detection-sensitivity of XFI for small animal studies
Summary
X-ray fluorescence imaging (XFI) is a non-invasive detection method of small quantities of elements, which can be excited to emit fluorescence x-ray photons upon irradiation with an incident x-ray beam. We present a synchrotron-based approach for reducing the minimal detectable marker concentration by demonstrating the feasibility of XFI for measuring the yet inaccessible distribution of the endogenous iodine in murine thyroids under in-vivo conform conditions. This result can be used as a reference case for the design of future preclinical XFI applications as mentioned above. When translating this technique from in-vitro to in-vivo, the increased sample thickness imposes a major challenge for separating the fluorescence signal from the multiple Compton scattering background This limits the sensitivity of XRF in the application of biomedical imaging, referred to as x-ray fluorescence imaging (XFI). Using measurements of rat thyroids as a r eference[29], the expected local iodine concentration is in the same order of magnitude as the expected marker concentrations in drug delivery and cell labeling s tudies[2], making the thyroid an interesting reference standard for determining the expected sensitivity of XFI for those applications
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