X-ray luminescence computed tomography via selective excitation: a feasibility study

Abstract

X-ray luminescence computed tomography (XLCT) is proposed as a new molecular imaging modality based on the selective excitation and optical detection of X-ray-excitable phosphor nanoparticles. These nano-sized particles can be fabricated to emit near-infrared (NIR) light when excited with X-rays, and, because because both X-rays and NIR photons propagate long distances in tissue, they are particularly well suited for in vivo biomedical imaging. In XLCT, tomographic images are generated by irradiating the subject using a sequence of programmed X-ray beams, while sensitive photo-detectors measure the light diffusing out of the subject. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the optical photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. This study presents computer simulations exploring the feasibility of imaging small objects with XLCT, such as research animals. The accumulation of 50 nm phosphor nanoparticles in a 2-mm-diameter target can be detected and quantified with subpicomolar sensitivity using less than 1 cGy of radiation dose. Provided sufficient signal-to-noise ratio, the spatial resolution of the system can be made as high as needed by narrowing the beam aperture. In particular, 1 mm spatial resolution was achieved for a 1-mm-wide X-ray beam. By including an X-ray detector in the system, anatomical imaging is performed simultaneously with molecular imaging via standard X-ray computed tomography (CT). The molecular and anatomical images are spatially and temporally co-registered, and, if a single-pixel X-ray detector is used, they have matching spatial resolution.

Fig. 1.

Depiction of the proposed XLCT system. A computer-controlled collimated X-ray beam selectively excites the sample while photo-detectors measure the light coming out.

Fig. 2.

Flowchart of the XLCT system simulation: The X-ray dose to the phantom is calculated by Monte-Carlo simulation using a map of the X-ray attenuation coefficients. The light produced by the nanophosphor is obtained by combining the X-ray ionization and the phosphor distribution map using (2). Finally, optical signal measured by the photo-detectors is computed from the optical sensitivity map as described in (3).

Fig. 3.

Optical sensitivity of the optical detection system as a function of source position for 802 nm light.

Fig. 4.

Multiple nanophosphor distributions were simulated inside a (a) 4.5-cm-diameter cylinder made of tissue-mimicking material. (b) Sensitivity phantom, comprising six 2-mm-diameter spheres, filled with phosphor concentrations of 0.1, 0.25, 0.5, 0.75, 1, and 2 μg/mL. (c) Lesion detectability phantom, consisting of six spheres, of diameter 0.25, 0.5, 1, 2, 4, and 8 mm, filled with phosphor concentrations of 1 μg/mL, inside a background nanophosphor concentration of 0.1 μg/mL. (d) Spatial resolution phantom, comprising six sets of rods, of diameter 0.5, 1, 1.5, 2, 3, and 4 mm.

Fig. 5.

(a) X-ray transmission scan reconstructed using filtered-backprojection. (b) Noise-free sinogram computed from the optical signal for the sensitivity phantom using 50 radial positions and 64 angles.

Fig. 6.

Reconstructed images for the sensitivity phantom, which comprises six spheres of diameter 2 mm, filled with nanophosphor concentrations of 0.1, 0.25, 0.5, 0.75, 1, and 2 μg/mL, embedded in the tissue-mimicking phantom, as a function of dose: (a) Noise-free simulation (unlimited dose); (b) noisy reconstruction assuming 100, (c) 10, and (d) 1 cGy to tissue.

Fig. 7.

Reconstructed nanophosphor concentration as a function of simulated concentration, for various levels of noise (noise-free, 1, 10, and 100 cGy). The dashed line represents the ideal concentration recovery.

Fig. 8.

Reconstructed images for the lesion detectability phantom, which comprises six spheres of diameter 0.25, 0.5, 1, 2, 4, and 8 mm, filled with phosphor concentrations of 1 μg/mL, embedded in the tissue-mimicking phantom, which contained a background nanophosphor concentration of 0.1 μg/mL, as a function of dose: (a) Noise-free simulation (unlimited dose); (b) noisy reconstruction assuming 100, (c) 10, and (d) 1 cGy to tissue.

Fig. 9.

Contrast-to-noise ratio (CNR), calculated as a function of sphere size and radiation dose. The dashed line represents Rose criterion [28].

Fig. 10.

Reconstructed images for the noise-free resolution phantom, which comprises multiple rods, of diameter 0.5, 1, 1.5, 2, 3, and 4 mm, embedded in the tissue-mimicking phantom, with no nanophosphor background. The projection sampling was (a) 50 × 64, (b) 50 × 128, (c) 100 × 64, and (d) 100 × 128 (angular × radial bins).