Experimental model validation for x-ray induced luminescence imaging in tissue phantoms with europium-doped nanophosphors

Objectives The goal of this study was to experimentally validate an imaging model for x-ray induced luminescence (XIL) based on the optical diffusion equation with appropriate boundary conditions. XIL imaging uses lanthanide-based nanoparticles (NPs) that emit near-infrared light in response to x-ray exposure; these NPs can potentially be used as in vivo photosensitizers or nanodosimeters. This work attempts to develop and validate an imaging model that relates observed surface radiance to NP distributions in tissue. Validation of this forward model is an important step towards solving the related inverse problem, which would allow for 3D in vivo molecular imaging with x-ray activated NPs.

Methods A diffuse optical gel phantom was fabricated with 1% agar, 1% Intralipid, and 0.005% black ink to mimic to optical scattering and absorption properties of near-infrared light in tissue. Europium-doped yttrium oxide (Y2O3:Eu3+) NPs were synthesized; spectroscopy measurements exhibited an XIL emission peak at 611 nm. 2 mg of NPs were injected into the tip of a capillary tube and inserted into the phantom at 1 cm below the imaging surface. A cooled CCD camera and macro lens captured the XIL image of the surface radiance using a small animal irradiator operating at 70 kVp tube voltage.

Results The luminescent point source of x-ray activated NPs at 1 cm depth produced a radially symmetric surface radiance. The signal intensity drop-off was measured with a line profile beginning at the center of the XIL signal. The proposed forward model is based on a Green’s function solution of the optical diffusion equation with extrapolated boundary conditions. When calculated for a luminescent point source a 1 cm depth in tissue with optical absorption µa=0.30 cm-1 and reduced scattering µ’s=10 cm-1 (the design parameters of the phantom), the model yielded a radial profile that agreed closely with the measured data. The approximated FWHM of the surface radiance is 1.2 cm for a point source of x-ray activated nanophosphors at 1 cm depth.

Conclusions XIL surface radiance measurements were successful in an optical tissue phantom using diagnostic energy level x-rays. The proposed imaging model agreed well with the measured surface radiance. When combined with selective plane illumination, the proposed imaging model reduced to a two-dimensional convolution and thus regularized deconvolution techniques will be investigated to improve the spatial resolution of the technique. $$graphic_E46FC0A7-5C04-4CB9-933D-FE3650A65626$$