Three-dimensional quantitative x-ray phase imaging

X-Ray Phase Contrast Imaging (XPCI) is one of the most exciting new methods emerged in x-ray science over recent years. It generates image contrast based on refraction and interference phenomena rather than x-ray attenuation, which enhances the visibility of all details in an image. Moreover, features classically considered "x-ray invisible" can be detected by XPCI. This has transformative power in many applications, from medicine to industrial testing, through biology, cultural heritage, material science, security inspections, and many other fields. It is worth remembering that the use of x-rays is all pervasive, both in science and in society, and all areas where x-ray imaging is used can strongly benefit from XPCI.

The problem up to a few years ago was that XPCI was considered restricted to large, specialized and expensive facilities called synchrotrons - only approximately 50 of which exist in the world. However, my research group has recently solved this problem by developing a method that enables XPCI to be performed with conventional x-ray sources, like those used in hospitals. This will allow taking XPCI out of ultra-specialized labs and into "real-world" applications, and negotiations with various companies are indeed underway to take the technology into commercial exploitation.

This project aims at developing the next generation of this technology. At the moment, our XPCI method works only in 2D, "planar" imaging applications. Although this is useful in itself, and is effectively employed in some areas (e.g. mammography or baggage scanning at airports), many other applications require the full 3D ("tomographic") reconstruction of the imaged sample. This is a well known problem in medicine, where for example some diseases cannot be diagnosed with a simple "x-ray" but require a CT (computed tomography) scan; the same principle also applies to many other areas, where full 3D knowledge of the sample is essential to the decision-making process that follows. Examples are in the development of new drugs, the effect of which is often assessed through high-resolution 3D images of the small animals on which they are tested, or in the testing of sophisticated mechanical parts or of new "composite" materials.

This project therefore aims at the development of a quantitative, full 3D version of our XPCI method. This requires overcoming a number of obstacles, some of which have a very technical nature. For example, in order to make x-ray imaging systems sensitive to x-ray phase, we use masks, which cover parts of the imaged object. Although this does not create a problem in planar imaging, because the portions of the sample which are covered are smaller than the smallest element the imaging system can resolve (the detector pixel), it does result in significant artifacts when a 3D volume is reconstructed, because of a problem known as undersampling. This is also encountered in other disciplines (for example nuclear medicine), and researchers have developed new, more sophisticated reconstruction tools which allow solving or at least mitigating this problem. We therefore plan to adapt these new reconstruction tools to the specific requirements of our XPCI method, so that reliable and quantitative 3D "phase" reconstruction can be performed.

Initially, this will be based on an extensive simulation phase during which different algorithms will be tested on various datasets, which will enable identifying the most promising ones. This will be followed by an experimental phase in which we will test the algorithms on real experimental data: this will allow selecting the best solution and fine-tuning it. Finally, there will be a demonstration phase in which the optimized 3D method will be applied to real scientific problems, among which for example the 3D visualization of small damage in articular cartilage (notoriously invisible to conventional x-ray methods), or of intrusion/defects in new-generation composite materials.

This project is expected to have significant impact, as it will substantially improve all applications of x-ray imaging. This is a direct consequence of the fact that, although sometimes overlooked, x-ray imaging is widely used in science and society. The main areas of impact include:

Medicine: in the long term, we aim at creating a step change in the early diagnosis of a wide variety of diseases, as well as in the planning/delivery/assessment of medical treatments. Our phase imaging methodologies can do this because they allow the visualization of features currently undetectable, which can enable the diagnosis of diseases at an earlier stage. This is of paramount importance in lethal diseases like cancer, as it can make the difference between a cancer that can be cured and one that cannot. However, early diagnosis is important also in non life-threatening diseases (e.g. one example that we will explicitly target is osteoarthritis), as treating a disease at an earlier stage can lead to a different evolution of the disease itself, and therefore to improved quality of life, with less need for constant care, etc. Beneficiaries include clinicians, who will have access to new diagnostic tools; the NHS, which will be able to reduce costs and provide better healthcare as a result of improved and less invasive diagnostic techniques; the medical industry, through the commercialization of the new technology, and, ultimately and most importantly, the patients.

Material science: we will provide a powerful new test tool for composite materials. These materials are the future workhorse of the aerospace and transport industries and are currently very difficult to test. The aerospace and transport sectors will benefit, but beneficiaries will also include manufacturers of test systems, Governmental bodies and the general public.
Another area that we will target is that of early detection of corrosion/porosity/fatigue cracks in a variety of materials. This will be beneficial to various industrial sectors, and include pathways to improved waste control. In general terms, the development of improved non-destructive testing tools will be of benefit to a variety of industrial products including microchips and other electronic components, pharmaceuticals, etc. It should be noted that better testing tools are also key to reduce the carbon footprint of all products.

Biology: we will produce phase-based 3D x-ray scanners which will enable new studies to be performed in conventional laboratories. This includes studies now possible only at synchrotrons. Some areas of cell biology, tissue studies to understand important diseases, etc are just a few examples in which the developed instruments will generate benefit not only to the scientific community, but also to the pharmaceutical industry and thus ultimately to the NHS and the patients. This also includes the development of new small-animal scanners with increased sensitivity.

Finally, companies active in the development and commercialization of scientific equipment will benefit from novel instrumentation developed in this project. Not only does this include manufacturers of x-ray sources, detectors, full imaging systems, etc but also companies active in the field of nanofabrication, and in particular microlithography, should the inclusion of apertured masks or similar devices become common practice in x-ray systems.