First demonstration of multiplexed X-ray fluorescence computed tomography (XFCT) imaging

Abstract

Simultaneous imaging of multiple probes or biomarkers represents a critical step toward high specificity molecular imaging. In this work, we propose to utilize the element-specific nature of the X-ray fluorescence (XRF) signal for imaging multiple elements simultaneously (multiplexing) using XRF computed tomography (XFCT). A 5-mm-diameter pencil beam produced by a polychromatic X-ray source (150 kV, 20 mA) was used to stimulate emission of XRF photons from 2% (weight/volume) gold (Au), gadolinium (Gd), and barium (Ba) embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The X-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used to isolate the K shell XRF peak and to generate sinograms for the three elements of interest. The distribution and concentration of the three elements were reconstructed with the iterative maximum likelihood expectation maximization algorithm. The linearity between the XFCT intensity and the concentrations of elements of interest was investigated. We found that measured XRF spectra showed sharp peaks characteristic of Au, Gd, and Ba. The narrow full-width at half-maximum (FWHM) of the peaks strongly supports the potential of XFCT for multiplexed imaging of Au, Gd, and Ba ( FWHM(Au,Kα1) = 0.619 keV, FWHM(Au,Kα2)=1.371 keV , FWHM(Gd,Kα)=1.297 keV, FWHM(Gd,Kβ)=0.974 keV , FWHM(Ba,Kα)=0.852 keV, and FWHM(Ba,Kβ)=0.594 keV ). The distribution of Au, Gd, and Ba in the water phantom was clearly identifiable in the reconstructed XRF images. Our results showed linear relationships between the XRF intensity of each tested element and their concentrations ( R(2)(Au)=0.944 , R(Gd)(2)=0.986, and R(Ba)(2)=0.999), suggesting that XFCT is capable of quantitative imaging. Finally, a transmission CT image was obtained to show the potential of the approach for providing attenuation correction and morphological information. In conclusion, XFCT is a promising modality for multiplexed imaging of high atomic number probes.

Fig. 1.

(a) Schematic illustration of the mechanism of XRF photon emission from K-shell electrons. (b) An XRF spectral fingerprint of Au excited by a monoenergetic radioisotope Tc99m (140 keV).

Fig. 2.

(a) Schematic diagram of the cylindrical water phantom with four conical tube insertions. (b) X-ray transmission images of the water phantom scanned with a cone-beam CT system (40 kV, 0.64 mA): anterior to posterior projection (left) and left lateral projection (right). The measured Hounsfield Unit (HU) for each component was water 7 HU, Au 1107 HU, Ba 1882 HU, Gd 1025 HU, and mixture 2768 HU. (c) Photographs of the cylindrical water phantom.

Fig. 3.

(a) Schematic of the experimental setup including the filtered X-ray source, the water phantom, and the CdTe detector. Multiplexing spectrum of Au, Gd, Ba, and Iodine (I) is show in the inset. The area under the dot line was the background photons derived from the Compton scatter. (b) Photograph of the imaging setup. A water phantom containing Au, Gd, and Ba insertions was moved on a rotation/translation stage while being irradiated by a narrow, filtered X-ray pencil beam. At each position, the XRF photons were collected with a CdTe detector.

Fig. 4.

A comparison of different filtered X-ray beams from the X-ray source operated at 150 keV, 20 mA. The Au K-edge energy is shown as a dotted line. Spectrum (D) was used for XFCT data acquisition.

Fig. 5.

A representative spectrum showing multiplexed detection in the water phantom containing a mixture of 2% Au, Gd, and Ba solutions.

Fig. 6.

Representative XRF spectra of three high-Z probes at two different concentrations: (a) Au (1% and 0.25%); (c) Gd (0.025% and 0.00625%); (e) Ba (0.75% and 0.375%). A linear relationship between the XRF intensity and the concentrations of the element solution was found.

Fig. 7.

Reconstructed XFCT multiplexed images of 2% (w/v) Au, Gd, and Ba solution embedded in a water phantom. (a) A photograph of the phantom, (b) multicolor overlay of the reconstructed XFCT image (red: Ba; blue: Au; green: Gd). (c) to (e) For the three elements of interest [(c) Au; (d) Ba; (e) Gd], XRF peaks in the spectra were processed into a sinogram for each element (left column) and reconstructed with ML-EM (right column).

Fig. 8.

Overlay of XFCT and X-ray transmission CT images of the phantom. Pseudo colors are used for different components in the XRF image: red for Ba; blue for Au; green for Gd.