Hybrid x-ray/optical luminescence imaging: characterization of experimental conditions

Abstract

Purpose: The feasibility of x-ray luminescence imaging is investigated using a dual-modality imaging system that merges x-ray and optical imaging. This modality utilizes x-ray activated nanophosphors that luminesce when excited by ionizing photons. By doping phosphors with lanthanides, which emit light in the visible and near infrared range, the luminescence is suitable for biological applications. This study examines practical aspects of this new modality including phosphor concentration, light emission linearity, detector damage, and spectral emission characteristics. Finally, the contrast produced by these phosphors is compared to that of x-ray fluoroscopy.

Methods: Gadolinium and lanthanum oxysulfide phosphors doped with terbium (green emission) or europium (red emission) were studied. The light emission was imaged in a clinical x-ray scanner with a cooled CCD camera and a spectrophotometer; dose measurements were determined with a calibrated dosimeter. Using these properties, in addition to luminescence efficiency values found in the literature for a similar phosphor, minimum concentration calculations are performed. Finally, a 2.5 cm agar phantom with a 1 cm diameter cylindrical phosphor-filled inclusion (diluted at 10 mg/ml) is imaged to compare x-ray luminescence contrast with x-ray fluoroscopic contrast at a superficial location.

Results: Dose to the CCD camera in the chosen imaging geometry was measured at less than 0.02 cGy/s. Emitted light was found to be linear with dose (R(2)= 1) and concentration (R(2)= 1). Emission peaks for clinical x-ray energies are less than 3 nm full width at half maximum, as expected from lanthanide dopants. The minimum practical concentration necessary to detect luminescent phosphors is dependent on dose; it is estimated that subpicomolar concentrations are detectable at the surface of the tissue with typical mammographic doses, with the minimum detectable concentration increasing with depth and decreasing with dose. In a reflection geometry, x-ray luminescence had nearly a 430-fold greater contrast to background than x-ray fluoroscopy.

Conclusions: X-ray luminescence has the potential to be a promising new modality for enabling molecular imaging within x-ray scanners. Although much work needs to be done to ensure biocompatibility of x-ray exciting phosphors, the benefits of this modality, highlighted in this work, encourage further study.

Figure 1

(a) Schematic of the experimental setup including the CCD camera, the x-ray source and detector, and the sample. (b) Photograph of the imaging setup.

Figure 2

(a) Radiation dose on the detector for three different configurations: (i) Direct irradiation, (ii) direct irradiation with lead shielding (5 mm on top, 50 mm on each side), and (iii) indirect irradiation with lead shielding. (b) Radiation events per area per dose.

Figure 3

(a) Emission spectra of GOS phosphors under x-ray excitation. GOS:Tb, with an emission peak at 545 nm, is labeled with asterisks (*), and GOS:Eu, with emission peaks at 596, 618, 627, and 707 nm. (b) X-ray induced GOS:Tb Photon output vs dose with dose varied by increasing tube current. (c) Photon output vs dose with dose varied by increasing irradiation time. For both methods, photon output is linear with dose shown in terms of current (r=1, p<0.001, R²=1). (d) Photon output vs concentration for the GOS:Eu phosphor. Concentrations were measured via microcuvette and dispersed in 1% agar. Photon output is linear with concentration (r=0.99, p=1.9×10⁻⁷).

Figure 4

Minimum estimated phosphor concentrations calculated from the literature and our own data. Lines represent phosphor luminescence efficiencies; the 100% line is based on efficiency data from a La₂O₂S:Tb phosphor reported by Kandarakis et al. (a) Minimum weight concentration (in mg/ml) vs dose (Gy). (b) Minimum molar concentration (in M) vs dose (Gy).

Figure 5

Agar imaging phantom with embedded phosphors and tissue emulating optical properties. (a) White-light optical image. (b) Projection fluoroscopy image (note the distinction between the phosphor inclusion—indicated by the arrow—around 300 units, compared to the black circle caused by a screw hole in the optical table supporting the phantom). (c) Optical emission from the phantom. (d) Overlay of the white light image (a) and the light emission (c).