Sensitivity evaluation and selective plane imaging geometry for x‐ray‐induced luminescence imaging

Abstract

Purpose X-ray induced luminescence (XIL) is a hybrid X-ray/optical imaging modality that employs nanophosphors that luminescence in response to X-ray irradiation. X-ray-activated phosphorescent nanoparticles have potential applications in radiation therapy as theranostics, nanodosimeters, or radiosensitizers. Extracting clinically relevant information from the luminescent signal requires the development of a robust imaging model that can determine nanophosphor distributions at depth in an optically scattering environment from surface radiance measurements. The applications of XIL in radiotherapy will be limited by the dose-dependent sensitivity at depth in tissue. We propose a novel geometry called selective plane XIL (SPXIL), and apply it to experimental measurements in optical gel phantoms and sensitivity simulations. Methods An imaging model is presented based on the selective plane geometry which can determine the detected diffuse optical signal for a given X-ray dose and nanophosphor distribution at depth in a semi-infinite, optically homogenous material. The surface radiance in the model is calculated using an analytical solution to the extrapolated boundary condition. Y2O3:Eu3+ nanoparticles are synthesized and inserted into various optical phantom in order to measure the luminescent output per unit dose for a given concentration of nanophosphors and calibrate an imaging model for XIL sensitivity simulations. SPXIL imaging with a dual-source optical gel phantom is performed, and an iterative Richardson-Lucy deconvolution using a shifted Poisson noise model is applied to the measurements in order to reconstruct the nanophosphor distribution. Results Nanophosphor characterizations showed a peak emission at 611 nm, a linear luminescent response to tube current and nanoparticle concentration, and a quadratic luminescent response to tube voltage. The luminescent efficiency calculation accomplished with calibrated bioluminescence mouse phantoms determines 1.06 photons were emitted per keV of X-ray radiation absorbed per g/mL of nanophosphor concentration. Sensitivity simulations determined XIL could detect a concentration of 1 mg/mL of nanophosphors with a dose of 1 cGy at a depth ranging from 2 to 4 cm, depending on the optical parameters of the homogeneous diffuse optical environment. The deconvolution applied to the SPXIL measurements could resolve two sources 1 cm apart up to a depth of 1.75 cm in the diffuse phantom. Conclusions We present a novel imaging geometry for XIL in a homogenous, diffuse optical environment. Basic characterization of Y2O3:Eu3+ nanophosphors are presented along with XIL/SPXIL measurements in optical gel phantoms. The diffuse optical imaging model is validated using these measurements and then calibrated in order to execute initial sensitivity simulations for the dose-depth limitations of XIL imaging. The SPXIL imaging model is used to perform a deconvolution on a dual-source phantom, which successfully reconstructs the nanophosphor distributions.

Focused x-ray luminescence imaging system for small animals based on a rotary gantry

“… 1 , 2 first reported a selective-excitation-based XLCT imaging and demonstrated that the distribution of deeply embedded contrast agents could be recovered with high-resolution and sensitivity with this method. Soon following, several research groups, including our own, improved several aspects of XLCT including the XLCT imaging systems, 3 – 13 robust reconstruction algorithms, 4 , 14 and designing efficient, bright, and biocompatible XLCT imaging probes. 15 – 20 …”

“…Another geometry is the fan or planar beam geometry, which can be used to image an entire cross-section at one time and allows for selective-planar imaging. 11 , 12 This method eliminates the need for raster scanning, which improves the imaging time; however, the lateral spatial resolution is degraded compared with the narrow beam selective excitation since the excitation is no longer localized to a small region but rather the entire cross-section. The last x-ray beam geometry is the conical-beam geometry, which offers the fastest scanning time of the three geometries mentioned since the object is entirely excited by the beam at one time.…”

Computational Approaches in Theranostics: Mining and Predicting Cancer Data

“…In silico approaches, including simulation and modelling [38,39,40,41,42,43,44,45,46,47,48], omics [49], and big data [2,48] have supported the tailored design of different therapeutic systems, such as nanoparticles, with optimized properties, providing fundamental knowledge on (1) the molecular basis of the therapeutic system and target cancer, (2) pharmacological performances and on (3) the complex interaction between the designed materials and the target systems [50].…”

Background luminescence in x-ray luminescence computed tomography (XLCT) imaging

“…fluorescence molecular tomography or bioluminescence optical tomography), this idea was extended to be able to reconstruct the three-dimensional distribution of luminescent particles in vivo through a hybrid molecular imaging modality called x-ray luminescence computed tomography (XLCT). Since XLCT was proposed, several groups including our own have made progress in demonstrating XLCT as a feasible imaging modality [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In principle, XLCT uses external high-energy x-ray photons that interrogate the object or specimen and embedded contrast agents (typically rare-earth doped nanophosphors such as GOS:Eu 3+ ) will emit optical photons.…”

“…Some of the emitted optical photons propagate to the object surface to be detected by highly sensitive photodetectors such as an electron multiplying charge-coupled device (EMCCD) camera or photomultiplier tubes (PMT) for optical tomographic image reconstruction. Different x-ray beam geometries have also been utilized for XLCT imaging, being first demonstrated with a narrow (pencil) beam geometry [3,4,11,12], but several groups have used other excitation geometries such as a conical beam [6][7][8][9][10] or sheet beam [19], each with their own advantages and disadvantages. Through this imaging principle, our group was able to demonstrate that XLCT was experimentally capable of submillimeter resolution [13,14,17] and capable of imaging GOS:Eu 3+ phosphor particle concentrations as low as 0.01 mg/mL (~27 μM) at scanning depths greater than 2 cm [15,16] using the narrow-beam x-ray geometry.…”