Experimental demonstration of direct L-shell x-ray fluorescence imaging of gold nanoparticles using a benchtop x-ray source

Purpose: To develop a proof-of-principle L-shell x-ray fluorescence (XRF) imaging system that locates and quantifies sparse concentrations of gold nanoparticles (GNPs) using a benchtop polychromatic x-ray source and a silicon (Si)-PIN diode x-ray detector system. Methods: 12-mm-diameter water-filled cylindrical tubes with GNP concentrations of 20, 10, 5, 0.5, 0.05, 0.005, and 0 mg/cm³ served as calibration phantoms. An imaging phantom was created using the same cylindrical tube but filled with tissue-equivalent gel containing structures mimicking a GNP-loaded blood vessel and approximately 1 cm³ tumor. Phantoms were irradiated by a 3-mm-diameter pencil-beam of 62 kVp x-rays filtered by 1 mm aluminum. Fluorescence/scatter photons from phantoms were detected at 90°with respect to the beam direction using a Si-PIN detector placed behind a 2.5-mm-diameter lead collimator. The imaging phantom was translated horizontally and vertically in 0.3-mm steps to image a 6 mm × 15 mm region of interest (ROI). For each phantom, the net L-shell XRF signal from GNPs was extracted from background, and then corrected for detection efficiency and in-phantom attenuation using a fluorescence-to-scatter normalization algorithm. Results: XRF measurements with calibration phantoms provided a calibration curve showing a linear relationship between corrected XRF signal and GNP mass per imaged voxel. Using the calibration curve, the detection limit (at the 95% confidence level) of the current experimental setup was estimated to be a GNP mass of 0.35 μg per imaged voxel (1.73 × 10^-2 cm³). A 2D XRF map of the ROI was also successfully generated, reasonably matching the known spatial distribution as well as showing the local variation of GNP concentrations. Conclusions: L-shell XRF imaging can be a highly sensitive tool that has the capability of simultaneously imaging the spatial distribution and determining the local concentration of GNPs presented on the order of parts-per-million level within subcentimeter-sized ex vivo samples and superficial tumors during preclinical animal studies.