Molecular imaging based on x-ray fluorescent high-Z tracers

Abstract

We propose a novel x-ray fluorescence imaging setup for the in vivo detection of high-Z tracer distributions. The main novel aspect is the use of an analyzer-based, energy-resolved detection method together with a radial, scatter reducing collimator. The aim of this work is to show the feasibility of this method by measuring the Bragg reflected K-fluorescence signal of an iodine solution sample in a proof of principle experiment and to estimate the potential of the complete imaging setup using a Monte Carlo simulation, including a quantification of the minimal detectable tracer concentration for in vivo imaging. The proof of principle experiment shows that even for a small detector area of approximately 7 mm(2), the collimated and Bragg reflected K-fluorescence signal of a sample containing an iodine solution with a concentration of 50 µg ml(-1) can be detected. The Monte Carlo simulation also shows that the proposed x-ray fluorescence imaging setup has the potential to image distributions of high-Z tracers in vivo at a radiation dose of a few mGy and at tracer concentrations down to 1 µg ml(-1) for iodine in small animals.

X-ray-Fluorescence Imaging for In Vivo Detection of Gold-Nanoparticle-Labeled Immune Cells: A GEANT4 Based Feasibility Study

“…The practical experience of our team with measurements of reference targets and dosimetry meets the results of these studies, such that the simulation error of Geant4 lies within reasonable limits, e.g., below 6 to 10% [21,23,25]. Furthermore, several GEANT4 simulation studies showed that the sensitivity of XFI in human-sized objects increased in the past decade [13,14,27].…”

“…However, clinical in vivo applications of XFI like molecular imaging with clinically available imaging modalities were not developed to date. This is mainly because the biggest problem for scanning big areas in human-sized objects is the high background due to multiple Compton scattering, which prevents fluorescence signals from being detected at reasonable marker concentrations [12,13]. This can, however, be counteracted in several ways, namely the use of a polarized incident X-ray beam, collimation, and by increasing the total detector area [12][13][14][15].…”

“…This is mainly because the biggest problem for scanning big areas in human-sized objects is the high background due to multiple Compton scattering, which prevents fluorescence signals from being detected at reasonable marker concentrations [12,13]. This can, however, be counteracted in several ways, namely the use of a polarized incident X-ray beam, collimation, and by increasing the total detector area [12][13][14][15]. Combining these technical countermeasures with a sophisticated signal analysis like a spatial filtering algorithm to determine the detector area with an ideal signal yield, as previously described [14], helps to further push the limits of XFI to enable in vivo imaging of human-sized objects.…”

Localising functionalised gold-nanoparticles in murine spinal cords by X-ray fluorescence imaging and background-reduction through spatial filtering for human-sized objects

“…in ref. 30 or our own previous work 31 . The second constraint is realised by using a set of molybdenum leaves, radially arranged around the beam, such that detected photons can only arise from within the scanning beam volume, effectively excluding higher-order Compton photons.…”

Focused anti-scatter grid for background reduction in x-ray fluorescence tomography

“…The grid can be designed in a number of ways, either linear or crossed, or planar or focused, and with different interspace and septa (grid bars) materials. Although one design using Bragg crystals has been proposed for XRF tomography [9], the setup is complex and results in a large loss of signal.…”