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Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation
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1. B. Koberle, M. T. Tomicic, S. Usanova, and B. Kaina, “Cisplatin resistance: Preclinical findings and clinical implications,” Biochim. Biophys. Acta 1806, 172182 (2010).
2. X. J. Liang, H. Meng, Y. Wang, H. He, J. Meng, J. Lu, P. C. Wang, Y. Zhao, X. Gao, B. Sun, C. Chen, G. Xing, D. Shen, M. M. Gottesman, Y. Wu, J. J. Yin, and L. Jia, “Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis,” Proc. Natl. Acad. Sci. U.S.A. 107, 74497454 (2010).
3. D. J. Stewart, “Mechanisms of resistance to cisplatin and carboplatin,” Crit. Rev. Oncol. Hematol. 63, 1231 (2007).
4. R. P. Perez, “Cellular and molecular determinants of cisplatin resistance,” Eur. J. Cancer 34, 15351542 (1998).
5. J. Chen, N. Emara, C. Solomides, H. Parekh, and H. Simpkins, “Resistance to platinum-based chemotherapy in lung cancer cell lines,” Cancer Chemother. Pharmacol. 66, 11031111 (2010).
6. P. J. Ferguson, “Mechanisms of resistance of human tumours to anticancer drugs of the platinum family: A review,” J. Otolaryngol. 24, 242252 (1995).
7. M. Harries and M. Gore, “Part II: Chemotherapy for epithelial ovarian cancer-treatment of recurrent disease,” Lancet Oncol. 3, 537545 (2002).
8. R. F. Ozols, “Ovarian cancer, Part II: Treatment,” Curr. Probl. Cancer 16, 61126 (1992).
9. S. K. Cheong, B. L. Jones, A. K. Siddiqi, F. Liu, N. Manohar, and S. H. Cho, “X-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticle-loaded objects using 110 kVp x-rays,” Phys. Med. Biol. 55, 647662 (2010).
10. B. L. Jones and S. H. Cho, “The feasibility of polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticle-loaded objects: A Monte Carlo study,” Phys. Med. Biol. 56, 37193730 (2011).
11. M. Bazalova, Y. Kuang, G. Pratx, and L. Xing, “Investigation of X-ray fluorescence computed tomography (XFCT) and K-Edge imaging,” IEEE Trans. Med. Imaging 31, 16201627 (2012).
12. L. A. Shepp and Y. Vardi, “Maximum likelihood reconstruction for emission tomography,” IEEE Trans. Med. Imaging 1, 113122 (1982).
13. P. P. Bruyant, “Analytic and iterative reconstruction algorithms in SPECT,” J. Nucl. Med. 43, 13431358 (2002).
14. G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: A feasibility study,” IEEE Trans. Med. Imaging 29, 19921999 (2010).
15. G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35, 33453347 (2010).
16. K. Lange and R. Carson, “EM reconstruction algorithms for emission and transmission tomography,” J. Comput. Assist. Tomogr. 8, 306316 (1984).
17. D. G. Lewis, “Optimization of a polarized source for in vivo x-ray fluorescence analysis of platinum and other heavy metals,” Phys. Med. Biol. 39, 197206 (1994).
18. R. Schmitz, A. Bingölbali, A. Hussain, and C. A. MacDonald, “Development of polarized and monochromatic x-ray beams from tube sources,” Proc. SPIE 7077, 70770Y170770Y8 (2008).
19. P. A. Ali, A. F. Al-Hussany, C. A. Bennett, D. A. Hancock, and A. M. El-Sharkawi, “Plane polarized x-ray fluorescence system for the in vivo measurement of platinum in head and neck tumours,” Phys. Med. Biol. 43, 23372345 (1998).
20. K. Ricketts, A. Castoldi, C. Guazzoni, C. Ozkan, C. Christodoulou, A. P. Gibson, and G. J. Royle, “A quantitative x-ray detection system for gold nanoparticle tumour biomarkers,” Phys. Med. Biol. 57, 55435555 (2012).
21. G. Jost, T. Mensing, S. Golfier, R. Lawaczeck, H. Pietsch, J. Hutter, L. Cibik, M. Gerlach, M. Krumrey, D. Fratzscher, V. Arkadiev, R. Wedell, M. Haschke, N. Langhoff, P. Wust, and L. Ludemann, “Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography,” Med. Phys. 36, 21072117 (2009).
22. H. v. Busch, G. Harding, G. Martens, J.-P. Schlomka, and B. Schweizer, “Investigation of externally activated x-ray fluorescence tomography for use in medical diagnostics,” Proc. SPIE 5745, 90101 (2005).
23. B. L. Jones, N. Manohar, F. Reynoso, A. Karellas, and S. H. Cho, “Experimental demonstration of benchtop x-ray fluorescence computed tomography (XFCT) of gold nanoparticle-loaded objects using lead- and tin-filtered polychromatic cone-beams,” Phys. Med. Biol. 57, N457N467 (2012).
24. J. Borjesson, M. Alpsten, S. Huang, R. Jonson, S. Mattsson, and C. Thornberg, “In vivo X-ray fluorescence analysis with applications to platinum, gold and mercury in man—Experiments, improvements, and patient measurements,” Basic Life Sci. 60, 275280 (1993).


Image of FIG. 1.

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FIG. 1.

(a) Schematic diagram of the cylindrical water phantom with four conical tube insertions. (b) Photograph of the cylindrical water phantom.

Image of FIG. 2.

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FIG. 2.

(a) Schematic of the experimental setup including the filtered x-ray source, water phantom, and CdTe detector. (b) Photograph of the imaging system setup. A water phantom containing different concentrations of cisplatin insertion 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. There were five lead bricks in Fig. 3(b) . The pencil beam was formed by the second and third lead bricks (from left to right in the figure), the other three bricks were used to block and shield the scatter from x-ray source.

Image of FIG. 3.

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FIG. 3.

A filtered x-ray beam was used for the XFCT imaging acquisition procedure. The x-ray source operated at 150 keV, 20 mA was filtered by a filter of 1 mm Pb, 7.3 mm Al, and 1.4 mm Cu. The Pt K-edge energy is shown as a vertical line. The peaks in the figure were Kα and Kβ peaks from the tungsten (W) in the x-ray tube (59 and 67 keV) as well as Kα and Kβ peaks from the lead (Pb) brick (72 and 74 keV).

Image of FIG. 4.

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FIG. 4.

Reconstructed image of the water phantom embedded with different concentrations of cisplatin. (Left) A diagram of the phantom; (middle) sinogram generated from XRF peaks of cisplatin in the acquired spectra; (right) reconstructed image using ML-EM algorithm.

Image of FIG. 5.

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FIG. 5.

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

Image of FIG. 6.

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FIG. 6.

Reconstructed XFCT multiplexed images of 2% (w/v) Pt, Gd, and I solution embedded in a water phantom. (a) A photograph of the phantom; (b) a diagram of the phantom showing the pseudocolors for different components in the XRF image; (c) XRF spectrum from one scanning position; (d) multicolor overlay of the reconstructed XFCT image (the spatial positions of different insertions in the water phantom – upper: I; lower: Gd; left: cisplatin; right: the mixture of these three elements). (e)–(g) For the three elements of interest [(e) Pt; (f) Gd; (g) I], XRF peaks in the spectra were processed into a sinogram (left column) for each element and reconstructed with ML-EM (right column).

Image of FIG. 7.

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FIG. 7.

Overlay of XFCT and x-ray transmission CT images of the phantom. Pseudocolors are used for different components in the XRF image. The spatial positions of different insertions in the water phantom – upper: I; lower: Gd; left: cisplatin; right: the mixture of these three elements. The measured Hounsfield unit (HU) for each component in the transmission CT was water 2 HU, Pt 1301 HU, I 1893 HU, Gd 1042 HU, and mixture 2241 HU.

Image of FIG. 8.

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FIG. 8.

The representative XRF spectra of two different concentrations: (a) Pt (0.36% and 0.18%, w/v); (c) Gd (0.05% and 0.003125%, w/v); (e) I (0.32% and 0.16%, w/v). A linear relationship between the XRF intensity and the concentrations of the element solution was found: (b) Pt (0.36%–0.18%, w/v); (d) Gd (0.05%–0.00078%, w/v); (f) I (3.2%–0.16%, w/v).


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Critical absorption and emission energies for photoelectric absorption and x-ray fluorescence emission.


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Developing an imaging method to directly monitor the spatial distribution of platinum-based (Pt) drugs at the tumor region is of critical importance for early assessment of treatment efficacy and personalized treatment. In this study, the authors investigated the feasibility of imaging platinum (Pt)-based drug distribution using x-ray fluorescence (XRF, a.k.a. characteristic x ray) CT (XFCT).


A 5-mm-diameter pencil beam produced by a polychromatic x-ray source equipped with a tungsten anode was used to stimulate emission of XRF photons from Pt drug 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 for the K-shell XRF peak isolation and sinogram generation for Pt. The distribution and concentration of Pt were reconstructed with an iterative maximum likelihood expectation maximization algorithm. The capability of XFCT to multiplexed imaging of Pt, gadolinium (Gd), and iodine (I) within a water phantom was also investigated.


Measured XRF spectrum showed a sharp peak characteristic of Pt with a narrow full-width at half-maximum (FWHM) (FWHMKα1 = 1.138 keV, FWHMKα2 = 1.052 keV). The distribution of Pt drug in the water phantom was clearly identifiable on the reconstructed XRF images. Our results showed a linear relationship between the XRF intensity of Pt and its concentrations (R 2 = 0.995), suggesting that XFCT is capable of quantitative imaging. A transmission CT image was also obtained to show the potential of the approach for providing attenuation correction and morphological information. Finally, the distribution of Pt, Gd, and I in the water phantom was clearly identifiable in the reconstructed images from XFCT multiplexed imaging.


XFCT is a promising modality for monitoring the spatial distribution of Pt drugs. The technique may be useful in tailoring tumor treatment regimen in the future.


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752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation