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

Abstract

Accurate in vivo localisation of minimal amounts of functionalised gold-nanoparticles, enabling e.g. early-tumour diagnostics and pharmacokinetic tracking studies, requires a precision imaging system offering very high sensitivity, temporal and spatial resolution, large depth penetration, and arbitrarily long serial measurements. X-ray fluorescence imaging could offer such capabilities; however, its utilisation for human-sized scales is hampered by a high intrinsic background level. Here we measure and model this anisotropic background and present a spatial filtering scheme for background reduction enabling the localisation of nanoparticle-amounts as reported from small-animal tumour models. As a basic application study towards precision pharmacokinetics, we demonstrate specific localisation to sites of disease by adapting gold-nanoparticles with small targeting ligands in murine spinal cord injury models, at record sensitivity levels using sub-mm resolution. Both studies contribute to the future use of molecularly-targeted gold-nanoparticles as next-generation clinical diagnostic and pharmacokinetic tools.

Design study for a compact laser-driven source for medical x-ray fluorescence imaging

“…where e and m e are the electron charge and mass, respectively, E 0 is the electric field amplitude of the laser, ω the laser frequency and c the speed of light. The photon energy radiated by an electron of velocity β and Lorentz factor γ is given by [65,66]: [5].…”

“…In our case, the bandwidth is the more crucial parameter. A too large bandwidth of the incident photon spectrum leads to a reduced sensitivity [5]. A lower photon number can theoretically be compensated with a larger number of shots per second.…”

“…Synchrotron radiation (SR) sources have the potential to deliver hard x-rays with high photon number and low bandwidth within a small divergence angle. This makes them an important research tool in many disciplines, including medical research where they could enable novel imaging modalities, such as x-ray fluorescence imaging (XFI) [1][2][3][4][5][6]. Being a scanning imaging modality, XFI explicitly requires pencil-beam geometries, as the spatial resolution is determined by the x-ray beam size.…”

“…Hard x-rays (90 keV) are required to excite the K α gold fluorescence and enable in-vivo imaging. Recently, human XFI imaging became feasible by overcoming its intrinsic Compton-background problem for large objects [5].…”

“…The required brilliant pencil beams are not easily realizable by clinical x-ray tubes with their highly divergent and broad spectrum [7]. There exist proof-of-concept XFI studies on synchrotrons [5]. However, as XFI is a scanning imaging modality (not like computed tomography using wide cone beams) it requires the ability of a source to scan a hemisphere from several angles, a condition which is not provided by large-scale synchrotrons.…”