# X-ray luminescence computed tomography
X-ray luminescence computed tomography (XLCT) is an imaging method that reconstructs the three-dimensional distribution of x-ray-excitable luminescent nanoparticles inside an object from optical measurements made at its surface. It combines two modalities: an x-ray beam that excites scintillating probes deep in the object, and optical detection of the emitted light at the surface. Because the x-ray excitation can be directed to a known position, probes can be excited selectively inside the object.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) A prototype system demonstrated the principle by imaging Gd2O2S:Eu phosphors in phantoms (test objects mimicking tissue for calibrating imaging)[2](https://opg.optica.org/ol/abstract.cfm?uri=ol-35-20-3345), and the reconstructed image represents the local concentration of the nanophosphor probe.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/)
| Key fact | Value |
|---|---|
| What is reconstructed | 3D concentration map of x-ray-excitable nanophosphor probes, from surface optical measurements[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) |
| Excitation mechanism | X-ray scintillators absorb x-ray energy and emit visible/NIR photons; x-rays penetrate deeply with minimal scattering[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) |
| Spatial resolution | Sub-millimeter with pencil beams (0.4 mm edge-to-edge separation resolved); about double the x-ray beam diameter; ~94 µm targeted with focused beams[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) |
| Scan time | Up to ~1 hour for pencil-beam scans; optical acquisition within two minutes for cone-beam XLCT, at reduced resolution[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) • [4](https://www.mdpi.com/2306-5354/11/9/874) |
| Sensitivity | A 21 mm deep target reconstructed at 0.01 mg/mL (27 µM) phosphor concentration; dose-dependent, with ng/mL recovery at therapy-level dosages[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) • [5](https://iopscience.iop.org/article/10.1088/0031-9155/56/12/003) |
| Typical probes | Gd2O2S:Eu (GOS:Eu), Y2O3:Eu, NaGdF4:Eu/Tb, CdTe quantum dots[2](https://opg.optica.org/ol/abstract.cfm?uri=ol-35-20-3345) • [1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) |
| Clinical status | All known scintillating probes are used only for preclinical and ex vivo imaging[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) |
## How it works
The contrast agents are x-ray scintillators: nanoparticles that absorb energy from x-ray photons and release part of it as visible or near-infrared light.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) Because an x-ray beam passes through tissue with minimal scattering, it can excite probes at a known, selectable location inside the object, and the emitted photons are collected by a sensitive camera at the surface.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) XLCT is thus a hybrid of x-ray CT and optical tomographic methods, exploiting nanophosphor probes that emit at discrete wavelengths across the visible-to-near-infrared range under x-ray irradiation.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/)
The forward model links the emitted light to the excitation. In the conventional formulation, the number of optical photons emitted is directly proportional to both the x-ray intensity distribution and the nanoparticle concentration, with light propagation described by a diffusion equation (with Robin boundary conditions, solved by finite elements).[4](https://www.mdpi.com/2306-5354/11/9/874) Later work showed that the luminescence of x-ray-excited nanophosphors depends more on the absorbed x-ray dose than on the x-ray intensity, motivating a dosage-based model in which the emitted optical power is proportional to the absorbed dose \( X_{d}(\mathbf{r}) \) in Gy and the phosphor concentration, with an energy-emission efficiency parameter \( \Gamma \) in W/(Gy·mg).[7](https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-23/issue-2/026006/Cone-beam-x-ray-luminescence-computed-tomography-based-on-x/10.1117/1.JBO.23.2.026006.pdf) The inverse problem, recovering the internal concentration from boundary measurements, is ill-posed because photons scatter strongly in biological tissue.[8](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.4790694)
## How it is done
An experiment proceeds from probe administration to tomographic reconstruction in these broad steps:
1. **Probe delivery.** The nanophosphor probe is introduced into the subject; early prototypes used europium-doped yttrium oxide (Y2O3:Eu), which scintillates at 611 nm and was synthesized in 10–100 nm sizes.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/)
2. **X-ray scanning.** A collimated or focused x-ray beam (or a cone beam covering the whole sample) is directed at the object from multiple angles. Excitation-resolved variants irradiate the same object at several tube voltages (55, 60, 65, 70, and 75 kV at 1 mA) to obtain spectral information about the probes.[9](https://remotesensing.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-20/issue-7/070501/Excitation-resolved-cone-beam-x-ray-luminescence-tomography/10.1117/1.JBO.20.7.070501.full)
3. **Optical detection.** Emitted photons are collected with an EMCCD camera (for example an Andor iXon DU-897 with 3 s integration and EM gain 260, behind a 4 mm lead shield), or, more cost-effectively for single-pixel measurements, photomultiplier tubes with gains around \( 10^{7} \).[9](https://remotesensing.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-20/issue-7/070501/Excitation-resolved-cone-beam-x-ray-luminescence-tomography/10.1117/1.JBO.20.7.070501.full) • [6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/)
4. **Reconstruction.** The measured surface fluxes are fit to a forward model. Early work used filtered back-projection and [maximum likelihood expectation maximization](https://www.edgepedia.org/maximum-likelihood-expectation-maximization) (MLEM) with a combined x-ray and light sensitivity matrix, recovering maps of nanoparticle location and concentration from only 14 angles over 180°.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/) Narrow-beam reconstructions solve an \( L_{1}/L_{q} \)-regularized problem \( \min_{x} \tfrac{1}{2} \| A x - b \|_{2}^{2} + \lambda \cdot R(x) \), where the x-ray beam position and size are included in the system matrix \( A \).[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) Cone-beam reconstructions use the diffusion approximation with sparse regularization, an incomplete variables truncated conjugate gradient method, and a permissible region strategy that reduced reconstruction error to less than 2 mm.[8](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.4790694) An \( L_{1} \)-regularized majorization–minimization algorithm adapted from [fluorescence molecular tomography](https://www.edgepedia.org/fluorescence-molecular-tomography) reconstructed four different probes with DICE similarity coefficients above 93% from six 30° projections at 50 kV, 1.0 mA.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/)
## Origin
XLCT was reported by Guillem Pratx and colleagues in 2010, in "X-Ray Luminescence Computed Tomography via Selective Excitation: A Feasibility Study" in IEEE Transactions on Medical Imaging.[10](https://doi.org/10.1109/tmi.2010.2055883) A companion 2010 paper in Optics Letters described the proof-of-concept prototype that imaged red-emitting Gd2O2S:Eu phosphors, which emit in the visible range around 620–630 nm, in various phantoms.[2](https://opg.optica.org/ol/abstract.cfm?uri=ol-35-20-3345) The method built on an earlier, non-tomographic technique: hybrid x-ray/optical luminescence imaging, characterized by [Carpenter](https://www.edgepedia.org/carpenter) and colleagues in Medical Physics in 2010, which showed that light emission from x-ray-activated nanophosphors is linear with dose (\( R^{2} = 1 \)) and concentration (\( R^{2} = 1 \)), and that in reflection geometry x-ray luminescence had nearly a 430-fold greater contrast to background than x-ray fluoroscopy.[11](https://doi.org/10.1118/1.3457332) • [12](https://pmc.ncbi.nlm.nih.gov/articles/PMC2917453/)
The main geometry variants followed quickly. Carpenter and colleagues described limited-angle x-ray luminescence tomography in Physics in Medicine and Biology in 2011.[13](https://doi.org/10.1088/0031-9155/56/12/003) Chen and colleagues proposed cone-beam XLCT in Medical Physics in 2013.[14](https://doi.org/10.1118/1.4790694) Cong and colleagues proposed focused-beam XLCT in dual-cone geometry in the Journal of Biomedical Optics in 2014.[15](https://doi.org/10.1117/1.jbo.19.7.076002) Xin Liu, Qimei Liao, and Hongkai Wang reported fast XLCT imaging in IEEE Transactions on Biomedical Engineering in 2014.[16](https://doi.org/10.1109/tbme.2013.2294633) Zhang and colleagues introduced a multiple-pinhole-collimator XLCT in Biomedical Optics Express in 2016[17](https://doi.org/10.1364/boe.7.002506) and a Bayesian-method cone-beam reconstruction was reported by Zhang and colleagues in IEEE Transactions on Medical Imaging in 2016.[18](https://doi.org/10.1109/tmi.2016.2603843)
## Variants
The choice of excitation geometry sets a resolution–speed trade-off. With a collimated x-ray pencil beam, XLCT resolved two targets with an edge-to-edge distance of 0.4 mm in 5 mm deep scattering media, and pencil-beam scans generally achieve sub-millimeter resolution using the beam size and position as structural guidance, but require long measurement times, typically up to 1 hour.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) Without a collimator, conical-beam XLCT achieves a location accuracy of about 1.5 mm but is much faster; cone-beam optical acquisition can complete within two minutes.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) • [4](https://www.mdpi.com/2306-5354/11/9/874) Published measurements indicate that XLCT spatial resolution is about double the x-ray beam diameter, and a focused beam provides three orders of magnitude higher photon density than a collimated beam.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) Sensitivity depends on dose: radiological doses recover µg/mL probe concentrations, while therapy dosages enable ng/mL recovery.[5](https://iopscience.iop.org/article/10.1088/0031-9155/56/12/003)
A comparative study of four XLCT contrast agents, commercial CdTe quantum dots, GOS:Eu microphosphor, and synthesized NaGdF4:Eu and NaGdF4:Tb nanophosphors, found GOS:Eu the brightest, with reconstructed intensity about 100–150 times greater than the others, attributed to its large particle size; brightness then decreased in the order NaGdF4:Tb, NaGdF4:Eu, and CdTe QDs.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/) That size is a double-edged property: GOS:Eu particles reach several micrometers, limiting in vivo use, while NaGdF4 nanoparticles have the highest in vivo potential because of their smaller size and functionalizability.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/)
Work published in 2024 addressed speed and reconstruction quality. DeepCB-XLCT, an end-to-end 3D encoder–decoder network with structural-similarity and region-of-interest losses, maps 2D surface measurements from 24 cone-beam angles directly to the 3D nanoparticle distribution; it resolves two targets with an edge-to-edge distance of 1.0 mm, supports three-target imaging, and outperformed ADFISTA, MAP, T-FISTA, and ADMLEM iterative methods in simulations, phantoms, and in vivo mouse experiments.[4](https://www.mdpi.com/2306-5354/11/9/874)
## Applications
XLCT has been applied to preclinical small-animal imaging: a cone-beam system was implemented by Chen and colleagues and applied to small animal imaging by Liu and colleagues.[7](https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-23/issue-2/026006/Cone-beam-x-ray-luminescence-computed-tomography-based-on-x/10.1117/1.JBO.23.2.026006.pdf) Multi-probe imaging is a distinctive capability: an excitation-resolved cone-beam scheme irradiated nanophosphors at 55–75 kV and applied principal component analysis to the reconstructed image sequence, resolving two nanophosphors (Y2O3:Eu3+ red and BaMgAl16O27:Eu2+ blue) with an edge-to-edge distance of 2.4 mm.[9](https://remotesensing.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-20/issue-7/070501/Excitation-resolved-cone-beam-x-ray-luminescence-tomography/10.1117/1.JBO.20.7.070501.full) Surgical guidance motivated the limited-angle work, which localized 2–14 mm lesions at 1–4.5 cm depth with a median error of 2.2 mm (4% of depth) in a breast-sized phantom simulating lumpectomy geometry.[5](https://iopscience.iop.org/article/10.1088/0031-9155/56/12/003) No human clinical use has been demonstrated; all known scintillating probes remain confined to preclinical and ex vivo imaging.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/)
## Limitations and alternatives
The central limitation is optical: photon scattering in biological tissue makes reconstruction of the 3D probe distribution an ill-posed problem, and cone-beam systems additionally rely on a first-order approximation of the radiative transfer equation, making the inverse problem ill-conditioned.[8](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.4790694) • [4](https://www.mdpi.com/2306-5354/11/9/874) Depth resolution degrades along the optical direction: recovered lesion size shows lower bias in the x-ray excitation direction than in the optical direction, which is expected from increased optical scatter.[5](https://iopscience.iop.org/article/10.1088/0031-9155/56/12/003) [Radiation](https://www.edgepedia.org/radiation) burden is geometry-dependent, spanning the typical range of a [CT scan](https://www.edgepedia.org/ct-scan) reported for multiple-pinhole imaging[17](https://doi.org/10.1364/boe.7.002506) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/) to higher levels measured for focused-beam scans.
Compared with [bioluminescence tomography](https://www.edgepedia.org/bioluminescence-tomography) and fluorescence molecular tomography, XLCT detects nanoparticle luminescence with an EMCCD camera and achieves greater imaging depth while avoiding autofluorescence background, since no endogenous signal competes with nanophosphor luminescence.[4](https://www.mdpi.com/2306-5354/11/9/874) • [6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/) With narrowly collimated pencil beams, its resolution can match the beam size (below 1 mm) with detection sensitivity comparable to fluorescence tomography, and x-ray excitation penetrates more deeply than laser light.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/) No demonstration of XLCT in human patients has been published, so clinical translation remains an open question.
## References
1. [Contrast agents for x-ray luminescence computed tomography](https://pmc.ncbi.nlm.nih.gov/articles/PMC10775909/)
2. [Tomographic molecular imaging of x-ray-excitable nanoparticles](https://opg.optica.org/ol/abstract.cfm?uri=ol-35-20-3345)
3. [Focused x-ray luminescence computed tomography: experimental studies](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105158/)
4. [Dual and Multi-Target Cone-Beam X-ray Luminescence Computed Tomography Based on the DeepCB-XLCT Network (Bioengineering 11(9):874, 2024; full text also at PMC11428951)](https://www.mdpi.com/2306-5354/11/9/874)
5. [Limited-angle x-ray luminescence tomography: methodology and feasibility study (Carpenter et al., 2011, Phys. Med. Biol.)](https://iopscience.iop.org/article/10.1088/0031-9155/56/12/003)
6. [Investigations on X-ray luminescence CT for small animal imaging](https://pmc.ncbi.nlm.nih.gov/articles/PMC3515210/)
7. [Cone-beam x-ray luminescence computed tomography based on x-ray absorption dosage (J. Biomed. Opt. 2018)](https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-23/issue-2/026006/Cone-beam-x-ray-luminescence-computed-tomography-based-on-x/10.1117/1.JBO.23.2.026006.pdf)
8. [Cone beam x-ray luminescence computed tomography: A feasibility study (Chen et al., 2013, Medical Physics)](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.4790694)
9. [Excitation-resolved cone-beam x-ray luminescence tomography (J. Biomed. Opt. 20(7):070501)](https://remotesensing.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-20/issue-7/070501/Excitation-resolved-cone-beam-x-ray-luminescence-tomography/10.1117/1.JBO.20.7.070501.full)
10. [Guillem Pratx and colleagues (2010). X-Ray Luminescence Computed Tomography via Selective Excitation: A Feasibility Study. IEEE Transactions on Medical Imaging.](https://doi.org/10.1109/tmi.2010.2055883)
11. [C. M. Carpenter and colleagues (2010). Hybrid x‐ray/optical luminescence imaging: Characterization of experimental conditions. Medical Physics.](https://doi.org/10.1118/1.3457332)
12. [Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions (Med Phys)](https://pmc.ncbi.nlm.nih.gov/articles/PMC2917453/)
13. [C M Carpenter and colleagues (2011). Limited-angle x-ray luminescence tomography: methodology and feasibility study. Physics in Medicine and Biology.](https://doi.org/10.1088/0031-9155/56/12/003)
14. [Dongmei Chen and colleagues (2013). Cone beam x‐ray luminescence computed tomography: A feasibility study. Medical Physics.](https://doi.org/10.1118/1.4790694)
15. [Wenxiang Cong and colleagues (2014). X-ray micromodulated luminescence tomography in dual-cone geometry. Journal of Biomedical Optics.](https://doi.org/10.1117/1.jbo.19.7.076002)
16. [Xin Liu, Qimei Liao, Hongkai Wang (2014). Fast X-Ray Luminescence Computed Tomography Imaging. IEEE Transactions on Biomedical Engineering.](https://doi.org/10.1109/tbme.2013.2294633)
17. [Wei Zhang and colleagues (2016). Multiple pinhole collimator based X-ray luminescence computed tomography. Biomedical Optics Express.](https://doi.org/10.1364/boe.7.002506)
18. [Guanglei Zhang and colleagues (2016). Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method. IEEE Transactions on Medical Imaging.](https://doi.org/10.1109/tmi.2016.2603843)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Clinical assessment and procedures › Medical imaging and radiography › Emerging and hybrid imaging modalities*
*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license