High resolution propagation-based imaging system for in vivo dynamic computed tomography of lungs in small animals.

We have developed an x-ray imaging system for in vivo four-dimensional computed tomography (4DCT) of small animals for pre-clinical lung investigations. Our customized laboratory facility is capable of high resolution in vivo imaging at high frame rates. Characterization using phantoms demonstrate a spatial resolution of slightly below 50 µm at imaging rates of 30 Hz, and the ability to quantify material density differences of at least 3%. We benchmark our system against existing small animal pre-clinical CT scanners using a quality factor that combines spatial resolution, image noise, dose and scan time. In vivo 4DCT images obtained on our system demonstrate resolution of important features such as blood vessels and small airways, of which the smallest discernible were measured as 55-60 µm in cross section. Quantitative analysis of the images demonstrate regional differences in ventilation between injured and healthy lungs.

Array-source X-ray velocimetry.

X-ray velocimetry (XV) has shown promise for investigations into various dynamic biological systems, including the motion of lungs and the flow of blood. Prior research in the field of XV has highlighted the need for both high spatial resolution to resolve features for tracking, and temporal resolution for accurate velocity measurement. In X-ray imaging systems, enhancement of spatial and temporal resolution requires a small focal spot size and high power output respectively, increasing anode power density requirements. In this paper, we present a multi-source XV regime whereby simultaneously illuminating a sample with multiple sources of small focal spot size, overall illumination can be increased whilst maintaining minimal source blurring without increasing power density requirements. Through a series of simulations, we demonstrate the capability for multi-source systems under various practical constraints, such as focal spot size and power density, to provide increased accuracy compared to single source systems.

Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge.

Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo.NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.

Phase contrast x-ray velocimetry of small animal lungs: optimising imaging rates.

Chronic lung diseases affect a vast portion of the world's population. One of the key difficulties in accurately diagnosing and treating chronic lung disease is our inability to measure dynamic motion of the lungs in vivo. Phase contrast x-ray imaging (PCXI) allows us to image the lungs in high resolution by exploiting the difference in refractive indices between tissue and air. Combining PCXI with x-ray velocimetry (XV) allows us to track the local motion of the lungs, improving our ability to locate small regions of disease under natural ventilation conditions. Via simulation, we investigate the optimal imaging speed and sequence to capture lung motion in vivo in small animals using XV on both synchrotron and laboratory x-ray sources, balancing the noise inherent in a short exposure with motion blur that results from a long exposure.

Decoding the structure of granular and porous materials from speckled phase contrast X-ray images.

Imaging techniques for studying the structure of opaque, granular and porous materials are limited by temporal resolution and radiation dose. We present a technique for characterising the structure of such materials by decoding three dimensional structural information from single, propagation based phase contrast X-ray images. We demonstrate the technique by measuring the distribution of diameters of glass microspheres in packed samples. We also present synthetic data, which shows that our inverse method is stable and that accuracy is improved by phase contrast X-ray imaging. Compared to computed tomography, our technique has superior temporal resolution and lower radiation dose.

Single-exposure dual-energy-subtraction X-ray imaging using a synchrotron source.

Projection radiography of the chest has long been plagued by the presence of bony anatomy obscuring visibility of the lungs and heart. Dual-energy subtraction is a well known method for differentiating bone and soft tissue, but existing techniques are not ideally suited to dynamic imaging. Herein a new technique to address this problem is presented. The harmonic content of a monochromated X-ray beam is exploited, and two in-line detectors are used to perform single-exposure dual-energy imaging. Images of a phantom demonstrate the ability to both separate and quantitatively measure the thickness of constituent materials, whilst images of a mouse thorax demonstrate the ability to separate bone and soft tissue in a biological specimen. The technique is expected to improve the performance of dynamic lung imaging.

Determining particle size distributions from a single projection image.

Imaging techniques employed to measure the structure of granular, particulate and porous materials are limited by scale, temporal resolution and, for biological samples, radiation exposure. This paper describes a technique for determining the distribution of particle sizes in opaque samples, for particle volume fractions less than ten percent, using a single projection radiograph. The method is based on the derived property of the additivity of the particles' spatial autocorrelation function in projection images. Simulations and experiments demonstrate the ability to use this property to determine the distribution of particle sizes in a material.

Interface-specific x-ray phase retrieval tomography of complex biological organs.

We demonstrate interface-specific propagation-based x-ray phase retrieval tomography of the thorax and brain of small animals. Our method utilizes a single propagation-based x-ray phase-contrast image per projection, under the assumptions of (i) partially coherent paraxial radiation, (ii) a static object whose refractive indices take on one of a series of distinct values at each point in space and (iii) the projection approximation. For the biological samples used here, there was a 9-200 fold improvement in the signal-to-noise ratio of the phase-retrieved tomograms over the conventional attenuation-contrast signal. The ability to 'digitally dissect' a biological specimen, using only a single phase-contrast image per projection, will be useful for low-dose high-spatial-resolution biomedical imaging of form and biological function in both healthy and diseased tissue.

Dynamic measures of regional lung air volume using phase contrast x-ray imaging.

Phase contrast x-ray imaging can provide detailed images of lung morphology with sufficient spatial resolution to observe the terminal airways (alveoli). We demonstrate that quantitative functional and anatomical imaging of lung ventilation can be achieved in vivo using two-dimensional phase contrast x-ray images with high contrast and spatial resolution (<100 microm) in near real time. Changes in lung air volume as small as 25 microL were calculated from the images of term and preterm rabbit pup lungs (n = 28) using a single-image phase retrieval algorithm. Comparisons with plethysmography and computed tomography showed that the technique provided an accurate and robust method of measuring total lung air volumes. Furthermore, regional ventilation was measured by partitioning the phase contrast images, which revealed differences in aeration for different ventilation strategies.

Fiber Bragg grating tether used to measure drag forces in neutral buoyancy flow tank tests.

The drag exerted on neutrally buoyant tethered spheres in a flow tank was measured as a function of flow rate. A unique solution to the problem was achieved using an optical fiber including a Bragg grating sensor as part of the tether. Measurements of the strain on the tether taken at flow rates between 0.14 and 0.33 m/s, were used to determine drag forces for spheres with diameters ranging from 40 to 100 mm. Vortex-induced vibration was observed in tests performed at Reynolds numbers from 5 x 10(3) to 4.5 x 10(4). The drag coefficients for these tests were found to range from 0.51 to 0.77.