Propagation-based Phase-contrast X-ray Imaging Research Articles

Precise phase retrieval for propagation-based images using discrete mathematics

The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.

Tomographic phase and attenuation extraction for a sample composed of unknown materials using x-ray propagation-based phase-contrast imaging.

Propagation-based phase-contrast x-ray imaging (PB-PCXI) generates image contrast by utilizing sample-imposed phase-shifts. This has proven useful when imaging weakly attenuating samples, as conventional attenuation-based imaging does not always provide adequate contrast. We present a PB-PCXI algorithm capable of extracting the x-ray attenuation β and refraction δ, components of the complex refractive index of distinct materials within an unknown sample. The method involves curve fitting an error-function-based model to a phase-retrieved interface in a PB-PCXI tomographic reconstruction, which is obtained when Paganin-type phase retrieval is applied with incorrect values of δ and β. The fit parameters can then be used to calculate true δ and β values for composite materials. This approach requires no a priori sample information, making it broadly applicable. Our PB-PCXI reconstruction is single-distance, requiring only one exposure per tomographic angle, which is important for radiosensitive samples. We apply this approach to a breast-tissue sample, recovering the refraction component δ, with 0.6-2.4% accuracy compared with theoretical values.

Phase-contrast X-ray tomography resolves the terminal bronchioles in free-breathing mice

Phase-contrast X-ray lung imaging has broken new ground in preclinical respiratory research by improving contrast at air/tissue interfaces. To minimize blur from respiratory motion, intubation and mechanical ventilation is commonly employed for end-inspiration gated imaging at synchrotrons and in the laboratory. Inevitably, the prospect of ventilation induced lung injury (VILI) renders mechanical ventilation a confounding factor in respiratory studies of animal models. Here we demonstrate proof-of-principle 3D imaging of the tracheobronchial tree in free-breathing mice without mechanical ventilation at radiation levels compatible with longitudinal studies. We use a prospective gating approach for end-expiration propagation-based phase-contrast X-ray imaging where the natural breathing of the mouse dictates the acquisition flow. We achieve intrapulmonary spatial resolution in the 30-μm-range, sufficient for resolving terminal bronchioles in the 60-μm-range distinguished from the surrounding lung parenchyma. These results should enable non-invasive longitudinal studies of native state murine airways for translational lung disease research in the laboratory.

In Silico Phase-Contrast X-Ray Imaging of Anthropomorphic Voxel-Based Phantoms

Propagation-based phase-contrast X-ray imaging is an emerging technique that can improve dose efficiency in clinical imaging. In silico tools are key to understanding the fundamental imaging mechanisms and develop new applications. Here, due to the coherent nature of the phase-contrast effects, tools based on wave propagation (WP) are preferred over Monte Carlo (MC) based methods. WP simulations require very high wave-front sampling which typically limits simulations to small idealized objects. Virtual anthropomorphic voxel-based phantoms are typically provided with a resolution lower than imposed sampling requirements and, thus, cannot be directly translated for use in WP simulations. In the present paper we propose a general strategy to enable the use of these phantoms for WP simulations. The strategy is based on upsampling in the 3D domain followed by projection resulting in high-resolution maps of the projected thickness for each phantom material. These maps can then be efficiently used for simulations of Fresnel diffraction to generate in silico phase-contrast X-ray images. We demonstrate the strategy on an anthropomorphic breast phantom to simulate propagation-based phase-contrast mammography using a laboratory micro-focus X-ray source.

Optimizing and applying high-resolution, in-line laboratory phase-contrast X-ray imaging for low-density material samples.

In-line, or propagation-based phase-contrast X-ray imaging (PBI) is an attractive alternative to the attenuation-based modality for low-density, soft samples showing low attenuation contrast. With the growing availability of micro- and nano-focus X-ray tubes, the method is increasingly applied in the laboratory. Here, we discuss the technique and demonstrate its advantages for selected low-density, low attenuation material samples using a lab-based micro- and nano-computed tomography systems Easytom XL Ultra, providing micron and sub-micron range resolution PBI images. We demonstrate a multi-step optimization of the lab-based PBI technique on our scanner that includes choosing the optimal detector-source hardware combination available in the setup, then optimizing the imaging geometry and finally the phase retrieval process through a parametric study. We point out and elaborate on the effect of noise correlation and texturing due to phase retrieval. We demonstrate the overall benefits of using the phase image and the phase retrieval for the selected samples such as improved image quality, increased contrast-to-noise ratio while only marginally influencing the spatial resolution. The improvement in image quality also enables further image processing steps for detailed structural analysis of the samples, which would be much more complicated if not impossible based on the transmissionimage.

Quantitative material decomposition using linear iterative near-field phase retrieval dual-energy x-ray imaging

This paper expands the linear iterative near-field phase retrieval (LIPR) formalism to achieve quantitative material thickness decomposition. Propagation-based phase contrast x-ray imaging with subsequent phase retrieval has been shown to improve the signal-to-noise ratio (SNR) by factors of up to hundreds compared to conventional x-ray imaging. This is a key step in biomedical imaging, where radiation exposure must be kept low without compromising the SNR. However, for a satisfactory phase retrieval from a single measurement, assumptions must be made about the object investigated. To avoid such assumptions, we use two measurements collected at the same propagation distance but at different x-ray energies. Phase retrieval is then performed by incorporating the Alvarez-Macovski (AM) model, which models the x-ray interactions as being comprised of distinct photoelectric and Compton scattering components. We present the first application of dual-energy phase retrieval with the AM model to monochromatic experimental x-ray projections at two different energies for obtaining split x-ray interactions. Our phase retrieval method allows us to separate the object investigated into the projected thicknesses of two known materials. Our phase retrieval output leads to no visible loss in spatial resolution while the SNR improves by factors of 2 to 10. This corresponds to a possible x-ray dose reduction by a factor of 4 to 100, under the Poisson noise assumption.

A phase-retrieval toolbox for X-ray holography and tomography.

Propagation-based phase-contrast X-ray imaging is by now a well established imaging technique, which - as a full-field technique - is particularly useful for tomography applications. Since it can be implemented with synchrotron radiation and at laboratory micro-focus sources, it covers a wide range of applications. A limiting factor in its development has been the phase-retrieval step, which was often performed using methods with a limited regime of applicability, typically based on linearization. In this work, a much larger set of algorithms, which covers a wide range of cases (experimental parameters, objects and constraints), is compiled into a single toolbox - the HoloTomoToolbox - which is made publicly available. Importantly, the unified structure of the implemented phase-retrieval functions facilitates their use and performance test on different experimental data.

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

Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X-ray (two modes) and fluorescence imaging (three modes) techniques for time-resolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X-ray) and/or (nano)particles (X-ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator-assisted aerosol inhalation. It is demonstrated that in vivo propagation-based phase-contrast X-ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue-cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and novel-designed NM for targeting and efficacy.

Comparison of quantitative multi-material phase-retrieval algorithms in propagation-based phase-contrast X-ray tomography

Propagation-based phase-contrast X-ray imaging provides high-resolution, dose-efficient images of biological materials. A crucial challenge is quantitative reconstruction, referred to as phase retr ...

Propagation-based Phase-Contrast X-ray Imaging at a Compact Light Source

We demonstrate the applicability of propagation-based X-ray phase-contrast imaging at a laser-assisted compact light source with known phantoms and the lungs and airways of a mouse. The Munich Compact Light Source provides a quasi-monochromatic beam with partial spatial coherence, and high flux relative to other non-synchrotron sources (up to 1010 ph/s). In our study we observe significant edge-enhancement and quantitative phase-retrieval is successfully performed on the known phantom. Furthermore the images of a small animal show the potential for live bio-imaging research studies that capture biological function using short exposures.

Real-time measurement of alveolar size and population using phase contrast x-ray imaging.

Herein a propagation-based phase contrast x-ray imaging technique for measuring particle size and number is presented. This is achieved with an algorithm that utilizes the Fourier space signature of the speckle pattern associated with the images of particles. We validate this algorithm using soda-lime glass particles, demonstrating its effectiveness on random and non-randomly packed particles. This technique is then applied to characterise lung alveoli, which are difficult to measure dynamically in vivo with current imaging modalities due to inadequate temporal resolution and/or depth of penetration and field-of-view. We obtain an important result in that our algorithm is able to measure changes in alveolar size on the micron scale during ventilation and shows the presence of alveolar recruitment/de-recruitment in newborn rabbit kittens. This technique will be useful for ventilation management and lung diagnostic procedures.

X-ray phase contrast with injected gas for tumor microangiography

We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas–tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research.

Feasibility study of propagation-based phase-contrast X-ray lung imaging on the Imaging and Medical beamline at the Australian Synchrotron

Propagation-based phase-contrast X-ray imaging (PB-PCXI) using synchrotron radiation has achieved high-resolution imaging of the lungs of small animals both in real time and in vivo. Current studies are applying such imaging techniques to lung disease models to aid in diagnosis and treatment development. At the Australian Synchrotron, the Imaging and Medical beamline (IMBL) is well equipped for PB-PCXI, combining high flux and coherence with a beam size sufficient to image large animals, such as sheep, due to a wiggler source and source-to-sample distances of over 137 m. This study aimed to measure the capabilities of PB-PCXI on IMBL for imaging small animal lungs to study lung disease. The feasibility of combining this technique with computed tomography for three-dimensional imaging and X-ray velocimetry for studies of airflow and non-invasive lung function testing was also investigated. Detailed analysis of the role of the effective source size and sample-to-detector distance on lung image contrast was undertaken as well as phase retrieval for sample volume analysis. Results showed that PB-PCXI of lung phantoms and mouse lungs produced high-contrast images, with successful computed tomography and velocimetry also being carried out, suggesting that live animal lung imaging will also be feasible at the IMBL.

Measurement of absolute regional lung air volumes from near-field x-ray speckles

Propagation-based phase contrast x-ray (PBX) imaging yields high contrast images of the lung where airways that overlap in projection coherently scatter the x-rays, giving rise to a speckled intensity due to interference effects. Our previous works have shown that total and regional changes in lung air volumes can be accurately measured from two-dimensional (2D) absorption or phase contrast images when the subject is immersed in a water-filled container. In this paper we demonstrate how the phase contrast speckle patterns can be used to directly measure absolute regional lung air volumes from 2D PBX images without the need for a water-filled container. We justify this technique analytically and via simulation using the transport-of-intensity equation and calibrate the technique using our existing methods for measuring lung air volume. Finally, we show the full capabilities of this technique for measuring regional differences in lung aeration.