Development of XFCT imaging strategy for monitoring the spatial distribution of platinum‐based chemodrugs: Instrumentation and phantom validation

Kuang, Yu; Pratx, Guillem; Bazalova, M.; Qian, Jing; Meng, Bao; Li, Xing

doi:10.1118/1.4789917

Cited by 35 publications

(40 citation statements)

References 32 publications

(28 reference statements)

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“…When electrons in the inner shells of the probes are removed via interactions with x-rays, characteristic x-ray fluorescent (XF) photons or Auger -electrons are emitted. Energy-resolving detectors can measure the XF photons which provides information about the distribution and concentration of the tracer agents in the target regions (Kuang et al 2014). Nanoparticles (NP) made for example from Au, Gd, Ba, I, or Hf are attractive labels for tracer molecules due to the highly penetrating XF radiation emitted from these elements.…”

Section: Introductionmentioning

confidence: 99%

“…Recent XFCT work by several groups (Pratx et al 2010, Cong et al 2011, Kuang et al 2013, Kuang et al 2014, Bazalova et al 2014, Ren et al 2014, Feng et al 2014, Ahmad, Bazalova, Xiang and Xing 2014, Ahmad, Pratx, Bazalova and Xing 2014, Sjölin and Danielsson 2014, Bazalova-Carter et al 2015, Ahmad et al 2015) have shown that XFCT can have theoretical molecular sensitivities down to 10 pM for 10 nm diameter AuNPs (Ahmad, Bazalova, Xiang and Xing 2014). Gold concentrations down to 2.5 mg/ml were experimentally detectable with a clinical x-ray source at 14 mGy in a proof of concept setup (Ahmad et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Feasibility study of Compton cameras for x-ray fluorescence computed tomography with humans

et al. 2016

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X-ray fluorescence imaging is a promising imaging technique able to depict the spatial distributions of low amounts of molecular agents in vivo. Currently, the translation of the technique to preclinical and clinical applications is hindered by long scanning times as objects are scanned with flux-limited narrow pencil beams. The study presents a novel imaging approach combining x-ray fluorescence imaging with Compton imaging. Compton cameras leverage the imaging performance of XFCT and abolish the need of pencil beam excitation. The study examines the potential of this new imaging approach on the base of Monte-Carlo simulations. In the work, it is first presented that the particular option of slice/fan-beam x-ray excitation has advantages in image reconstruction in regard of processing time and image quality compared to traditional volumetric Compton imaging. In a second experiment, the feasibility of the approach for clinical applications with tracer agents made from gold nano-particles is examined in a simulated lung scan scenario. The high energy of characteristic x-ray photons from gold is advantageous for deep tissue penetration and has lower angular blurring in the Compton camera. It is found that Doppler broadening in the first detector stage of the Compton camera adds the largest contribution on the angular blurring; physically limiting the spatial resolution. Following the analysis of the results from the spatial resolution test, resolutions in the order of one centimeter are achievable with the approach in the center of the lung. The concept of Compton imaging allows to distinguish to some extend between scattered photons and x-ray fluorescent photons based on their difference in emission position. The results predict that molecular sensitivities down to 240 pM/l for 5 mm diameter lesions at 15 mGy for 50 nm diameter gold nano-particles are achievable. A 45-fold speed up time for data acquisition compared to traditional pencil beam XFCT could be achieved for lung imaging on cost of a small sensitivity decrease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility study of Compton cameras for x-ray fluorescence computed tomography with humans

et al. 2016

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“…Especially, in our latest experimental study, 7 we demonstrated the capability of performing benchtop XFCT of GNPloaded objects using polychromatic cone-beams, paving the way to build a practical benchtop XFCT system. Additionally, other researchers have applied similar benchtop XFCT techniques to image various other metal probes (e.g., platinum) within small-animal-sized phantoms, [9][10][11] suggesting the possibility of extending benchtop XFCT techniques beyond GNP applications.…”

Section: Introductionmentioning

confidence: 99%

Improving x‐ray fluorescence signal for benchtop polychromatic cone‐beam x‐ray fluorescence computed tomography by incident x‐ray spectrum optimization: A Monte Carlo study

2014

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Purpose: To develop an accurate and comprehensive Monte Carlo (MC) model of an experimental benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) setup and apply this MC model to optimize incident x-ray spectrum for improving production/detection of x-ray fluorescence photons from gold nanoparticles (GNPs). Methods: A detailed MC model, based on an experimental XFCT system, was created using the Monte Carlo N-Particle (MCNP) transport code. The model was validated by comparing MC results including x-ray fluorescence (XRF) and scatter photon spectra with measured data obtained under identical conditions using 105 kVp cone-beam x-rays filtered by either 1 mm of lead (Pb) or 0.9 mm of tin (Sn). After validation, the model was used to investigate the effects of additional filtration of the incident beam with Pb and Sn. Supplementary incident x-ray spectra, representing heavier filtration (Pb: 2 and 3 mm; Sn: 1, 2, and 3 mm) were computationally generated and used with the model to obtain XRF/scatter spectra. Quasimonochromatic incident x-ray spectra (81, 85, 90, 95, and 100 keV with 10 keV full width at half maximum) were also investigated to determine the ideal energy for distinguishing gold XRF signal from the scatter background. Fluorescence signal-to-dose ratio (FSDR) and fluorescence-normalized scan time (FNST) were used as metrics to assess results. Results: Calculated XRF/scatter spectra for 1-mm Pb and 0.9-mm Sn filters matched (r ≥ 0.996) experimental measurements. Calculated spectra representing additional filtration for both filter materials showed that the spectral hardening improved the FSDR at the expense of requiring a much longer FNST. In general, using Sn instead of Pb, at a given filter thickness, allowed an increase of up to 20% in FSDR, more prominent gold XRF peaks, and up to an order of magnitude decrease in FNST. Simulations using quasimonochromatic spectra suggested that increasing source x-ray energy, in the investigated range of 81-100 keV, increased the FSDR up to a factor of 20, compared to 1 mm Pb, and further facilitated separation of gold XRF peaks from the scatter background. Conclusions: A detailed MC model of an experimental benchtop XFCT system has been developed and validated. In exemplary calculations to illustrate the usefulness of this model, it was shown that potential use of quasimonochromatic spectra or judicious choice of filter material/thickness to tailor the spectrum of a polychromatic x-ray source can significantly improve the performance of benchtop XFCT, while considering trade-offs between FSDR and FNST. As demonstrated, the current MC model is a reliable and powerful computational tool that can greatly expedite the further development of a benchtop XFCT system for routine preclinical molecular imaging with GNPs and other metal probes. C

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“…[1][2][3] This technique is based on x-ray excitation of imaging probes containing high-Z elements followed by fluorescence x-ray emission. The energy of the fluorescence x-ray is characteristic to the high-Z element, and it is measured with an energy-resolving photon-counting detector.…”

Section: Introductionmentioning

confidence: 99%

Proton‐induced x‐ray fluorescence CT imaging

et al. 2015

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Purpose: To demonstrate the feasibility of proton-induced x-ray fluorescence CT (pXFCT) imaging of gold in a small animal sized object by means of experiments and Monte Carlo (MC) simulations. Methods: First, proton-induced gold x-ray fluorescence (pXRF) was measured as a function of gold concentration. Vials of 2.2 cm in diameter filled with 0%-5% Au solutions were irradiated with a 220 MeV proton beam and x-ray fluorescence induced by the interaction of protons, and Au was detected with a 3 × 3 mm 2 CdTe detector placed at 90• with respect to the incident proton beam at a distance of 45 cm from the vials. Second, a 7-cm diameter water phantom containing three 2.2-diameter vials with 3%-5% Au solutions was imaged with a 7-mm FWHM 220 MeV proton beam in a first generation CT scanning geometry. X-rays scattered perpendicular to the incident proton beam were acquired with the CdTe detector placed at 45 cm from the phantom positioned on a translation/rotation stage. Twenty one translational steps spaced by 3 mm at each of 36 projection angles spaced by 10• were acquired, and pXFCT images of the phantom were reconstructed with filtered back projection. A simplified geometry of the experimental data acquisition setup was modeled with the MC TOPAS code, and simulation results were compared to the experimental data. Results: A linear relationship between gold pXRF and gold concentration was observed in both experimental and MC simulation data (R 2 > 0.99). All Au vials were apparent in the experimental and simulated pXFCT images. Specifically, the 3% Au vial was detectable in the experimental [contrast-to-noise ratio (CNR) = 5.8] and simulated (CNR = 11.5) pXFCT image. Due to fluorescence x-ray attenuation in the higher concentration vials, the 4% and 5% Au contrast were underestimated by 10% and 15%, respectively, in both the experimental and simulated pXFCT images.

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Development of XFCT imaging strategy for monitoring the spatial distribution of platinum‐based chemodrugs: Instrumentation and phantom validation

Cited by 35 publications

References 32 publications

Feasibility study of Compton cameras for x-ray fluorescence computed tomography with humans

Feasibility study of Compton cameras for x-ray fluorescence computed tomography with humans

Improving x‐ray fluorescence signal for benchtop polychromatic cone‐beam x‐ray fluorescence computed tomography by incident x‐ray spectrum optimization: A Monte Carlo study

Proton‐induced x‐ray fluorescence CT imaging

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