In vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source

Abstract

We describe the first dynamic and the first in vivo X-ray imaging studies successfully performed at a laser-undulator-based compact synchrotron light source. The X-ray properties of this source enable time-sequence propagation-based X-ray phase-contrast imaging. We focus here on non-invasive imaging for respiratory treatment development and physiological understanding. In small animals, we capture the regional delivery of respiratory treatment, and two measures of respiratory health that can reveal the effectiveness of a treatment; lung motion and mucociliary clearance. The results demonstrate the ability of this set-up to perform laboratory-based dynamic imaging, specifically in small animal models, and with the possibility of longitudinal studies.

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

“…PB‐PCXI utilizes differences in X‐ray refractive index and associated phase shifts at air–tissue interfaces for enhancing soft tissue contrast (e.g., in the lung) as compared to X‐ray absorption . Building on our previously published in vivo PB‐PCXI studies in murine lungs, the present study demonstrates that combined in vivo PB‐PCXI and ex vivo fluorescence imaging can provide complementary information, which enhances the understanding of complex processes such as NM/NP delivery to the lung in a quantitative way on various scales (whole lung to cellular). The strengths and weaknesses of all five imaging modalities used here are summarized with respect to 2D/3D imaging capability, resolution, fidelity (conservation of original anatomical 3D structure), anatomical information, and technical complexity as summarized in Table .…”

“…Also, quantitative imaging of co‐localization of tumor associated macrophages with therapeutic 64 Cu‐labeled polyglucose nanoparticle in an orthotopic model of lung adenocarcinoma was accomplished via PET, in vivo confocal microscopy, and tissue‐cleared LSFM . PCXI has already been applied for ex vivo and in vivo studies on mucociliary transport of large microparticles or 5–100 µm fibers in the trachea or upper airways of animal models such as mice and pigs and for monitoring the delivery of liquids to murine lungs via nose or intubated cannula delivery . Moreover, several common bulk particulates (e.g., lead dust, quarry dust, glass beads, asbestos, and Galena with size ≥ 5 µm) were tracked in live animal trachea airways by PCXI, showing the high variability in particle movement during mucociliary transport .…”

“…For “nasal aspiration,” a similar protocol was applied as reported by Gradl et al Briefly, a mixture of polystyrene NPs (1:10 dilution) and gold NP (1:2 dilution) suspensions was loaded into a syringe pump mentioned above, permitting controlled liquid delivery outside the imaging hutch. Here 80 µL of the polystyrene‐gold liquid mixture was spontaneously inhaled via the nose by the mouse.…”

“…Consequently, the penetration depth of light, sensitivity, and quantification ability offered by PA imaging are not sufficient for determination of NM biodistribution and pharmacodynamics in the lungs. X‐ray‐based approaches (PCXI and CT) have been recently applied to monitor the pulmonary fluid delivery dynamics and deposition and lung pathophysiological state with high temporal and spatial resolution. The major challenges posed by X‐ray modalities are that they are incapable of assessing NM bioactivity and for visualizing NM at cellular resolution.…”

A compact light source providing high-flux, quasi-monochromatic, tunable X-rays in the laboratory

“…19,20 The MuCLS has been operating with a high degree of uptime since then and has enabled many scientific experiments and publications. [21][22][23][24][25][26][27][28][29][30][31] Generally, most X-ray techniques such as diffraction, imaging, spectroscopy or scattering can be performed with both electron-impact and synchrotron sources. While the details depend on the technique and the specific application needs, generally the following guidelines apply: Longer measurement times Shorter measurement times Lower resolution and sensitivity Higher resolution and sensitivity Suitable where fixed energy or polychromatic beam is acceptable Required where tunability and/or monochromaticity is required Advantageous for large sample sizes (e.g., imaging of large components and low or moderate resolution)…”