Karen Siu

Dynamic imaging of the lungs using x-ray phase contrast

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.

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.

Computed tomographic x-ray velocimetry

An x-ray velocimetry technique is described which provides three components of velocity measurement in three dimensional space. Current x-ray velocimetry techniques, which use particle images taken at a single projection angle, are limited to two components of velocity measurement, and are unable to measure in three dimensions without a priori knowledge of the flow field. The proposed method uses multiple projection angles to overcome these limitations. The technique uses a least-squares iterative scheme to tomographically reconstruct the three-dimensional velocity field directly from two-dimensional image pair cross-correlations, without the need to reconstruct three-dimensional particle images. Synchrotron experiments demonstrate the effectiveness of the technique for blood flow measurement in opaque vessels, with applications for the diagnosis and treatment of cardiovascular disease.

Wavelet-based feature extraction applied to small-angle x-ray scattering patterns from breast tissue: a tool for differentiating between tissue types

This paper reports on the application of wavelet decomposition to small-angle x-ray scattering (SAXS) patterns from human breast tissue produced by a synchrotron source. The pixel intensities of SAXS patterns of normal, benign and malignant tissue types were transformed into wavelet coefficients. Statistical analysis found significant differences between the wavelet coefficients describing the patterns produced by different tissue types. These differences were then correlated with position in the image and have been linked to the supra-molecular structural changes that occur in breast tissue in the presence of disease. Specifically, results indicate that there are significant differences between healthy and diseased tissues in the wavelet coefficients that describe the peaks produced by the axial d-spacing of collagen. These differences suggest that a useful classification tool could be based upon the spectral information within the axial peaks.

Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS)

Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm(-1). Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity.

Computed Tomographic X‐ray Velocimetry

An X‐ray velocimetry technique is described which provides three components of velocity measurement in three‐dimensional space. Current X‐ray velocimetry techniques, which use particle images taken at a single projection angle, are limited to two components of velocity measurement, and are unable to measure in three dimensions without a priori knowledge of the flow field. The proposed method uses multiple projection angles to overcome these limitations. The technique uses a least‐squares iterative scheme to tomographically reconstruct the three‐dimensional velocity field directly from two‐dimensional image pair cross‐correlations, without the need to reconstruct three‐dimensional particle images. Synchrotron experiments demonstrate the effectiveness of the technique for blood flow measurement in opaque vessels, with applications for the diagnosis and treatment of cardiovascular disease.

Analyser-based phase contrast image reconstruction using geometrical optics

Analyser-based phase contrast imaging can provide radiographs of exceptional contrast at high resolution (<100 microm), whilst quantitative phase and attenuation information can be extracted using just two images when the approximations of geometrical optics are satisfied. Analytical phase retrieval can be performed by fitting the analyser rocking curve with a symmetric Pearson type VII function. The Pearson VII function provided at least a 10% better fit to experimentally measured rocking curves than linear or Gaussian functions. A test phantom, a hollow nylon cylinder, was imaged at 20 keV using a Si(1 1 1) analyser at the ELETTRA synchrotron radiation facility. Our phase retrieval method yielded a more accurate object reconstruction than methods based on a linear fit to the rocking curve. Where reconstructions failed to map expected values, calculations of the Takagi number permitted distinction between the violation of the geometrical optics conditions and the failure of curve fitting procedures. The need for synchronized object/detector translation stages was removed by using a large, divergent beam and imaging the object in segments. Our image acquisition and reconstruction procedure enables quantitative phase retrieval for systems with a divergent source and accounts for imperfections in the analyser.

Towards the clinical application of X-ray phase contrast imaging

Synchrotron-based propagation-based imaging, a type of phase contrast imaging, produces better soft tissue image contrast than conventional radiography. To determine whether the technique is directly transferable to the clinical environment for routine diagnostic or screening imaging, a micro-focus (100 microm spot-size) Molybdenum X-ray source with 0.03 mm molybdenum filtration was installed at a local hospital. Breast tissue samples, excised masses and mastectomies, were obtained directly from surgery and imaged at three geometries. The first geometry was optimised for visualizing phase contrast effects using a ray-line argument, the second was the same as that employed by Konica-Minolta in their commercial phase contrast system, and the third was the conventional contact arrangement. The three images taken of each tissue sample were comparatively scored in a pair-wise fashion. Scoring was performed by radiologist expert in mammography, general radiologists, associated clinicians and radiographers on high-resolution mammography rated monitors at two separate locations. Scoring indicated that the optimised and Konica geometries both outperformed the conventional mammographic geometry. An unexpected complication within the trial was the effect that the scoring platform and the associated display tools had on some of the scorers responses. Additionally, the trial revealed that none of the conventional descriptors for image quality were adequate in the presence of phase contrast enhancements.

Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.

Animals In Synchrotrons: Overcoming Challenges For High‐Resolution, Live, Small‐Animal Imaging

Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live‐animal synchrotron X‐ray imaging studies. Our group has extensive experience in high‐resolution live‐animal imaging at the Japanese SPring‐8 synchrotron, primarily examining airways in two‐dimensions. These experiments normally image an area of 1.8 mm×1.2 mm at a pixel resolution of 0.45 μm and are performed with live, intact, anaesthetized mice.There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small‐animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, and deliver test substances while collecting images. The horizontal synchrotron X‐ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions‐of‐interest slow and can result in a high radia...