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X-ray fluorescence molecular imaging (XFMI) has shown great promise as a low-cost molecular imaging modality for clinical and pre-clinical applications with high sensitivity. Recently, progress has been made in enabling the XFMI technique with laboratory X-ray sources for various biomedical applications. However, the sensitivity of XFMI still needs to be improved for in vivo biomedical applications at a reasonably low radiation dose. In laboratory X-ray source-based XFMI, the main factor that limits the molecular sensitivity of XFMI is the scatter X-rays that coincide with the fluorescence X-rays from the targeted material. In this paper, we experimentally investigated the effects of excitation beam spectrum on the molecular sensitivity of XFMI, by quantitatively deriving minimum detectable concentration (MDC) under a fixed surface entrance dose of 200 mR at three different excitation beam spectra. XFMI experiments were carried out on two customized mouse-sized phantoms. The result shows that the MDC can be readily increased by a factor of 5.26 via excitation spectrum optimization. Furthermore, a numerical model was developed and validated by the experimental data. The numerical model can be used to optimize XFMI system configurations to further improve the molecular sensitivity. Findings from this investigation could find applications for in vivo pre-clinical small-animal XFMI in the future.

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Improving Molecular Sensitivity in X-Ray Fluorescence Molecular Imaging (XFMI) of Iodine Distribution in Mouse-Sized Phantoms via Excitation Spectrum Optimization