Using X-ray velocimetry to measure lung function and assess the efficacy of a pseudomonas aeruginosa bacteriophage therapy for cystic fibrosis.

Phase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases such as cystic fibrosis (CF), particularly with increasing rates of multi-drug-resistant infections.

Correcting directional dark field x-ray imaging artefacts using position dependent image deblurring and attenuation removal.

In recent years, a novel x-ray imaging modality has emerged that reveals unresolved sample microstructure via a "dark-field image", which provides complementary information to conventional "bright-field" images, such as attenuation and phase-contrast modalities. This x-ray dark-field signal is produced by unresolved microstructures scattering the x-ray beam resulting in localised image blur. Dark-field retrieval techniques extract this blur to reconstruct a dark-field image.

Ultra-fastdirectional dark-field x-ray imaging for visualising magnetic control of particles for airway gene delivery.

Magnetic nanoparticles can be used as a targeted delivery vehicle for genetic therapies. Understanding how they can be manipulated within the complex environment of live airways is key to their application to cystic fibrosis and other respiratory diseases.Dark-field x-ray imaging provides sensitivity to scattering information, and allows the presence of structures smaller than the detector pixel size to be detected.

X-ray phase and dark-field computed tomography without optical elements.

X-ray diffusive dark-field imaging, which allows spatially unresolved microstructure to be mapped across a sample, is an increasingly popular tool in an array of settings. Here, we present a new algorithm for phase and dark-field computed tomography based on the x-ray Fokker-Planck equation. Needing only a coherent x-ray source, sample, and detector, our propagation-based algorithm can map the sample density and dark-field/diffusion properties of the sample in 3D.

Noncontact Respiratory Motion Detection in Anesthetized Rodents.

Small animal physiology studies are often complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron radiation facilities. This is because these facilities are typically not designed specifically for biomedical research, and the animals and image detectors are located away from the researchers in a radiation enclosure. In respiratory X-ray imaging studies one challenge is the detection of respiration in free-breathing anaesthetised rodents, to enable images to be acquired at specific phases of the breath and for detecting changes in respiratory rate.

On the quantification of sample microstructure using single-exposure x-ray dark-field imaging via a single-grid setup.

The size of the smallest detectable sample feature in an x-ray imaging system is usually restricted by the spatial resolution of the system. This limitation can now be overcome using the diffusive dark-field signal, which is generated by unresolved phase effects or the ultra-small-angle x-ray scattering from unresolved sample microstructures. A quantitative measure of this dark-field signal can be useful in revealing the microstructure size or material for medical diagnosis, security screening and materials science.

Directional dark-field retrieval with single-grid x-ray imaging.

Directional dark-field imaging is an emerging x-ray modality that is sensitive to unresolved anisotropic scattering from sub-pixel sample microstructures. A single-grid imaging setup can be used to capture dark-field images by looking at changes in a grid pattern projected upon the sample. By creating analytical models for the experiment, we have developed a single-grid directional dark-field retrieval algorithm that can extract dark-field parameters such as the dominant scattering direction, and the semi-major and -minor scattering angles.

X-Ray Dark-Field and Phase Retrieval Without Optics, via the Fokker-Planck Equation.

Emerging methods of x-ray imaging that capture phase and dark-field effects are equipping medicine with complementary sensitivity to conventional radiography. These methods are being applied over a wide range of scales, from virtual histology to clinical chest imaging, and typically require the introduction of optics such as gratings. Here, we consider extracting x-ray phase and dark-field signals from bright-field images collected using nothing more than a coherent x-ray source and a detector.

Multimodal intrinsic speckle-tracking (MIST) to extract images of rapidly-varying diffuse X-ray dark-field.

Speckle-based phase-contrast X-ray imaging (SB-PCXI) can reconstruct high-resolution images of weakly-attenuating materials that would otherwise be indistinguishable in conventional attenuation-based X-ray imaging. The experimental setup of SB-PCXI requires only a sufficiently coherent X-ray source and spatially random mask, positioned between the source and detector. The technique can extract sample information at length scales smaller than the imaging system's spatial resolution; this enables multimodal signal reconstruction.

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.

Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging.

Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturally spread to the alveoli during inspiration, and therapeutic particles of any form are rapidly cleared via mucociliary transit.

Quantifying the x-ray dark-field signal in single-grid imaging.

X-ray dark-field imaging reveals the sample microstructure that is unresolved when using conventional methods of x-ray imaging. In this paper, we derive a new method to extract and quantify the x-ray dark-field signal collected using a single-grid imaging set-up, and relate the signal strength to the number of sample microstructures, N. This was achieved by modelling sample-induced changes to the shadow of the upstream grid, and fitting experimental data to this model.

Dark-field tomography of an attenuating object using intrinsic x-ray speckle tracking.

We investigate how an intrinsic speckle tracking approach to speckle-based x-ray imaging is used to extract an object's effective dark-field (DF) signal, which is capable of providing object information in three dimensions. The effective DF signal was extracted using a Fokker-Planck type formalism, which models the deformations of illuminating reference beam speckles due to both coherent and diffusive scatter from the sample. Here, we assumed that (a) small-angle scattering fans at the exit surface of the sample are rotationally symmetric and (b) the object has both attenuating and refractive properties.

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.

Material decomposition from a single x-ray projection via single-grid phase contrast imaging.

This study describes a new approach for material decomposition in x-ray imaging, utilizing phase contrast both to increase sensitivity to weakly attenuating samples and to act as a complementary measurement to attenuation, therefore allowing two overlaid materials to be separated. The measurements are captured using the single-exposure, single-grid x-ray phase contrast imaging technique, with a novel correction that aims to remove propagation-based phase effects seen at sharp edges in the attenuation image. The use of a single-exposure technique means that images can be collected in a high-speed sequence.

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry.

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung.

Towards automated in vivo tracheal mucociliary transport measurement: Detecting and tracking particle movement in synchrotron phase-contrast x-ray images.

Accurate in vivo quantification of airway mucociliary transport (MCT) in animal models is important for understanding diseases such as cystic fibrosis, as well as for developing therapies. A non-invasive method of measuring MCT behaviour, based on tracking the position of micron sized particles using synchrotron x-ray imaging, has previously been described. In previous studies, the location (and path) of each particle was tracked manually, which is a time consuming and subjective process.

Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source.

Most measures of lung health independently characterise either global lung function or regional lung structure. The ability to measure airflow and lung function regionally would provide a more specific and physiologically focused means by which to assess and track lung disease in both pre-clinical and clinical settings. One approach for achieving regional lung function measurement is via phase contrast X-ray imaging (PCXI), which has been shown to provide highly sensitive, high-resolution images of the lungs and airways in small animals.

Model-Based Iterative Reconstruction for Propagation-Based Phase-Contrast X-Ray CT including Models for the Source and the Detector.

Propagation-based phase-contrast X-ray computed tomography is a valuable tool for high-resolution visualization of biological samples, giving distinct improvements in terms of contrast and dose requirements compared to conventional attenuation-based computed tomography. Due to its ease of implementation and advances in laboratory X-ray sources, this imaging technique is increasingly being transferred from synchrotron facilities to laboratory environments. This however poses additional challenges, such as the limited spatial coherence and flux of laboratory sources, resulting in worse resolution and higher noise levels.

Methods for dynamic synchrotron X-ray respiratory imaging in live animals.

Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges.