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Postgraduate and honours research projects - X-ray imagingPhase contrast imaging of marsupial lung over the perinatal periodDr Karen Siu (Monash Centre for Synchrotron Science/School of Physics) Assoc Prof Peter Frappell (Department of Zoology, Latrobe University) Although the marsupial foetus is born after only 4 weeks gestation and lives external of the womb from day 28 of development to maturity, the marsupial neonate displays some special adaptations for external life including well-developed forelimbs, a functional mesonephric kidney and precociously developed lungs and associated air passages. The observation that the highly underdeveloped marsupial neonate has functional lungs is in stark contrast to the observation that premature birth of eutherian neonates is complicated by lung failure. At birth, the wallaby lung is at a stage of development equivalent to a 22 week old human foetus. Thus the majority of lung development occurs outside the uterus whilst the joey is in the pouch and easily accessible by the researcher. Additionally wallaby lung development occurs slowly - it takes approximately 6 months for the lungs to develop to a stage equivalent to human lungs at birth. For these reasons the wallaby is an excellent model for studying the key changes in mammalian lung development. These will be characterised using X-ray phase contrast imaging which renders visible details of lungs that are completely invisible on conventional absorption X-radiographs. This project will seek quantitative measures of lung development from synchrotron phase contrast images and CT and contrast these with biomechanical measures and imaging of the cellular structure. For further information please contact:
Dr Karen Siu Counting nephrons using a synchrotron
Dr Karen Siu (Monash Centre for Synchrotron Science/School of Physics) Total nephron number in the kidney is an important guide of kidney development and an important marker of risk for hypertension in adult life. In humans, nephrogenesis (formation of nephrons) is completed by 36 weeks of gestation. A number of foetal environmental perturbations as well as gene mutations or haplo-insufficiencies have been shown to result in reduced nephron number. Indeed, we have shown that total nephron number in humans ranges from approximately 200,000 to more than 2 million. It is important to develop optimised methods for nephron counting. The Bertram Group in the Department of Anatomy and Cell Biology is internationally recognised for the use of the physical disector/fractionator combination (gold standard in unbiased stereological nephron counting) however, this method is slow, tedious and very expensive. A new methodology is required. This project, suitable for students with either a physics and/or a biomedical background, will assess the feasibility of a novel synchrotron-based technique, Phase Contrast X-ray Imaging (PCXI) to provide a faster and hence more efficient estimate of nephron number. The physics component of this project will include assessment of contrast agents for optimal glomerular visualisation using PCXI, carrying out synchrotron imaging experiments (as practicable) and development of image processing methods for automated nephron recognition and counting from 3D x-ray imaging data. The anatomy component of this project will involve preparation of mouse kidneys suitable for imaging, and post-processing for embedding into methacrylate resin for counting using the traditional disector-fractionator method to estimate nephron number and comparison with PCXI. For further information please contact:
Dr Karen Siu Phase contrast tomosynthesis: a potential tool for in vivo assessment of cystic fibrosis therapies
Dr Karen Siu (Monash Centre for Synchrotron Science/School of Physics) Cystic Fibrosis (CF) causes chronic, progressive, infective and inflammatory lung disease that begins in childhood and eventually leads to death in early adulthood. This project is part of an exciting wider study led by Dr David Parsons at the Women's and Children's Hospital, Adelaide, that is developing airway gene transfer for CF gene therapy. Gene therapy offers real hope for curing this often debilitating and early fatal disease, but its effectiveness, longevity and safety have yet to be established. Unlike conventional X-ray imaging, synchrotron-based phase contrast (PC) imaging has the ability to reveal the soft tissues with extremely high resolution and is proposed as a non-invasive, in vivo method of assessing the effectiveness of CF gene therapies. When coupled with computed tomography (CT), this technique can provide excellent three dimensional visualisation of the airways. However, CT at the high resolutions necessary to observe the terminal airways of the lungs is extremely time consuming and hence unsuitable for in vivo applications, as it involves the acquisition of many hundreds or thousands of single images. This project will investigate the use of tomosynthesis techniques with synchrotron based PC imaging to form a new PC imaging modality that maintains the ability to generate cross sectional images at depth, but requiring far fewer images. This resulting reduction in radiation dose would make this modality extremely attractive for in vivo imaging. For further information please contact:
Dr Karen Siu Imaging tumor cells in an animal model of malignant brain tumorDr Chris Hall (Monash Centre for Synchrotron Science) Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumour in humans. Despite multimodal treatment including surgery, radiotherapy and chemotherapy, the high rate of tumor recurrence results in a very poor prognosis. Existing imaging methods allow detection of the primary tumour, once it reaches a certain size, but fail to show the residual tumoral microaggregates left behind following treatment. We have devised an x-ray imaging protocol that allows detection of small numbers of implanted glioma cells in an animal brain. The protocol is based on using nanometric gold particles as markers embodied within the cell by endocytosis. The research project is in its early stages. So far we have taken C6 glioma cell cultures which were exposed to colloidal gold. These were implanted into the brains of rats. After the tumours had developed for two weeks x-ray images of the heads and spinal chords were acquired at a synchrotron x-ray imaging station using absorption microtomography. The results so far show that the contrast enhanced tumours was clearly visible in the resulting images. The next steps in the research will be to calculate the limiting parameters for this technique. We believe that synchrotron-based imaging in animal models could become a powerful research tool in the assessment of brain tumour volume and growth. This work is directly relevant to the new Australian Synchrotron which has been built right next to the Monash campus in Clayton. However at the moment the dose delivered during this microtomography technique is high. A thorough analysis of the existing data is required as well as some modelling and calculations of dose. You will learn to use an open source imaging application (ImageJ) to examine the ‘slices’ of the data. Using this you will calculate the attenuation for known tissues which will be compared with a database. The attenuation for the contrast enhanced tissue will then be calculated. Using this information and a model system you will calculate the x-ray flux required to see the contrast enhanced cells for various x-ray wavelengths. A similar calculation for a different type of tomographic imaging will be made. That of fluorescence tomography. A technique which will work with the same gold nanoparticles. For further information please contact:
Dr Chris Hall Contrast imaging for assessment of microvascular blood flow in the post-infarction heartDr James Pearson (Department of Physiology, Monash University) When a blood clot or a fatty plaque dislodges and blocks a major artery in the wall of the heart irreversible damage to a large region of the heart wall can occur unless blood flow is rapidly restored. Following a heart attack (myocardial infarction) the blood supply to the cardiac muscle is frequently compromised in regions beyond the initial blockage due to circulating factors that constrict blood vessels. Currently in this laboratory we are undertaking a large project utilizing synchrotron imaging to evaluate a novel therapy for preventing heart failure by preserving normal coronary blood flow in the infarcted heart. Clinical MRI and x-ray imaging does not have either the spatial or temporal resolution to detect and accurately measure microvessels in the beating heart. We have been using synchrotron radiation contrast angiography to visualise the microvessels in the heart following an injection of iodine solution into an artery. However, new analytical approaches are required to quantify blood flow and velocity in these microvessels to investigate the efficacy of therapies to prevent heart failure. This project is suitable for biomedical, physics and engineering students with an interest in developing and testing new imaging techniques that will benefit cardiovascular medicine. Dependent on background this project will involve image analysis and or implementing new contrast imaging techniques. For further information please contact:
Dr James Pearson Biomedical imaging with laser generated x-ray sourcesDr Chris Hall (Monash Centre for Synchrotron Science) X-rays have been used in medical imaging with great success for many years. The first x-ray radiograph was made back in 1895 by Wilhelm Conrad Roentgen. It was an image of his wife's hand. Despite the huge increase in the use of x-ray radiography in modern times the technology behind the generation of x-rays for medical imaging has changed very little. Almost all sources in hospitals use accelerated electrons which are steered onto a metal target for x-ray production. However, within the last few years the technologies developed for high power lasers and also in compact particle accelerators has come together to create a new source of x-ray photons which appears very suitable for biomedical imaging. It has long been known that longer wavelength lower energy photons can scatter from fast moving charged particles. The momentum imparted to the photon in the scatter results in greatly decreased wavelength (increased energy). This 'inverse Compton' scattering process can be exploited for x-ray production. A beam of high energy electrons is generated and infra-red or optical photons are scattered from them. The result is the production of a highly collimated beam of x-rays. The availability of compact linear electron accelerators today, and very powerful optical lasers means inverse Compton scatter is now a practical way to generate x-rays for imaging. Sources which make use of this idea have recently been made available commercially: http://www.mxisystems.com/ourmachines.html. The MCSS x-ray biomedical imaging research group is interested in using the characteristics of x-rays produce by these types of sources. The four outstanding qualities they provide are their brightness, essential for rapid radiographic exposures. The fast pulsed nature of the emission of the x-rays which can be utilised for ballistic imaging. The small size of the x-ray source which gives phase contrast possibilities, and the fact that their spectrum can be changed very rapidly which might be utilised in spectroscopic imaging. None of these aspects have been thoroughly researched with respect to the implications for medical and biomedical imaging. MCSS has a strategic link with Vanderbilt University in the USA and the Australian commercial supplier of the machines Regional Health Care Group). This project will look at the potential of such sources and test the ideas on real apparatus including the Australian Synchrotron Imaging and Therapy beam line, which is due to commence operations in early 2009. For further information please contact:
Dr Chris Hall Lung Disease Detection using Phase Contrast X-ray Imaging
Dr Marcus Kitchen (School of Physics), Phase contrast X-ray imaging greatly enhances the visibility of the air-filled lung over attenuation contrast alone. This imaging technique is able to resolve the very smallest of terminal respiratory units (alveoli; <100 micrometers) as they fill with air. Since phase contrast is highly sensitive to density variations within the lung we hypothesise that it will be sensitive to pathological changes associated with lung disease. We aim to determine the potential for phase contrast X-ray imaging as a diagnostic tool for detecting lung disease, such as pulmonary fibrosis and emphysema, during the early pathogenic phase. Mouse models of lung disease will be imaged using phase contrast imaging techniques using highly coherent synchrotron radiation. This project will involve the development of imaging techniques to enhance in the detection of lung disease. For example, we will be exploring the using of Particle Image Velocimetry (PIV) for tracking variations in shear stresses in the lungs due to changes in tissue compliance associated with lung disease. We will also be investigating methods of numerically segmenting lung images to remove the ribcage from lung images to assist with disease detections. This will involve developing new imaging techniques alongside an appropriate mathematical framework to enable image segmentation. Image processing will form a major component of the project, with the ultimate aim of developing computer assisted disease detection from phase contrast images of the lung. Computer simulations will also be employed to model the imaging systems for optimization of the imaging setup for disease detection. For more information, please contact:
Dr Marcus Kitchen
Associate Professor Stuart Hooper Measuring Lung Aeration at Birth using Phase Contrast X-ray Imaging
Dr Marcus Kitchen (School of Physics), Before birth, the future airways of the lung are filled with liquid which must be cleared at the time of birth to allow the entry of air and the initiation of air-breathing. This process is critical for the transition to pulmonary gas exchange at birth and is markedly impaired in infants born very premature. As a result, respiratory failure at birth is the greatest cause of morbidity and mortality in newborn infants. Synchrotron-based phase contrast x-ray imaging has made it possible to visualise and measure the rate and spatial pattern of lung aeration in animals in real-time, from birth. The very high spatial resolution allows us to visualise the smallest terminal respiratory units (alveoli; <100 micrometers) as they fill with air. We have developed phase retrieval algorithms that accurately calculate total lung air volumes from these 2D images and have validated them using a plethysmograph. As a result, we can now accurately measure, on a breath-by-breath basis, lung air volumes within different regions of the lungs from two-dimensional phase contrast x-ray images. This project aims to refine this technique to enable quantitative local measures of regional lung air volume. This will enable us to determine how to safely aerate the lungs of preterm infants that require mechanical ventilation without inducing lung injury; a significant problem faced in the neonatal ward. For more information, please contact:
Dr Marcus Kitchen
Associate Professor Stuart Hooper 3D Measurement of Blood Flow using Computed Tomographic X-ray PIV
Dr Andreas Fouras (Biological Engineering), Vascular disease is the leading cause of death and disability in the developed world. Due to our aging population, the burden of this disease is expected to continue to grow over coming decades. There is an increasing appreciation of the importance of vascular fluid dynamics, shear and rheology in the genesis of vascular disease. However, the details of the relationship between properties of vascular flow, and the processes of vascular disease remain ill-defined. One of the key barriers to the progression of our understanding of these factors is the inability to make detailed measurements of vascular flow in any but the thinnest or most transparent of vessels. Medical imaging techniques that have previously been used to measure flows in vivo, such as ultrasonography and MRI, are generally restricted to velocity field measurements with spatial resolutions of millimetre precision. Imaging techniques which are known to measure velocity data with resolution of blood elements or better are restricted by a lack of optical access. New emerging synchrotron CT X-ray PIV techniques, pioneered at Monash, offer the ability to investigate blood flow in 3D to very high resolution, offering new quantitative insights into cardiovascular processes. The project will entail implementing CT X-ray PIV using synchrotron X-ray technology to measure 3D, time resolved, biological flows in vivo. The successful candidate will be required to design the experimental setup and procedures. Additionally analysis of the obtained data will be required to determine the rheological flow conditions, and thus the biological implications on the vessels. Applications should demonstrate a strong interest in developing cutting edge techniques for biomedical applications. Research will be conducted in a multidisciplinary team consisting of synchrotron scientists, physiologists and biomedical engineers. For further information on this project please contact:
Andreas Fouras Measurement Of Lung Damage Using X-Ray PIV
Dr Andreas Fouras (Biological Engineering), A. Prof. Stuart Hooper (Physiology), Within the womb, foetal lungs are filled with liquid which must be cleared at birth to allow the entry of air and to initiate respiration. This process is remarkably impaired in infants born very premature, leaving their lungs not ready to function. Clinically, the required response to this impairment is mechanical ventilation. Currently mechanical ventilation of preterm infant lungs induces a high occurrence of lung injury; a significant problem faced in the neonatal ward. New emerging synchrotron X-ray PIV techniques, pioneered at Monash, offer the ability to investigate blood flow in 3D to very high resolution, offering new quantitative insights to enable us to determine how to safely aerate preterm lungs by use of mechanical ventilators. The project will entail implementing X-ray PIV using synchrotron X-ray technology to measure lung function in vivo. The successful candidate will be required to design the experimental setup and procedures. Additional analysis of the data will be required to determine strain induced in lung tissue as a result of different ventilation strategies. Applicants should demonstrate a strong interest in developing cutting edge techniques for biomedical applications. The successful candidate will work in a team of engineers, physicists and physiologists, and be involved in synchrotron experiments. For further information on this project please contact:
Andreas Fouras |