Phase modulation technology for X-ray imaging

Lead Research Organisation: University College London
Department Name: London Centre for Nanotechnology


We plan to develop coherence-based X-ray imaging methods, which have great potential for solving a wide range of physical problems and are expected to see wide usership, especially at Diamond's I13 beamline. Coherence is a relatively new addition to the capabilities of synchrotron facilities and not all of its applications have been explored. There is much to learn by transferring technology from existing visible-light capabilities, as we plan. Gratings for X-rays, which need high aspect ratio and small (50-nanometer) feature sizes, can be manufactured on site at Harwell. Grating-based measurement techniques are in the early stages of development and will be developed under this proposal for the benefit of the materials and biological imaging communities.Microfabrication has always played an important role in modern x-ray imaging. From the 1952 proposal by Albert Baez to use Fresnel zone plates to build an x-ray microscope, x-ray imagers have profited from the rapid advances in the microfabrication industry. X-ray zone plates are now the key technology for x-ray microscopes. The modern practice of making them by electron-beam writing was pioneered by the MIT and IBM groups in the early eighties and can now deliver soft X-ray zone plates with an outer zone width (which roughly equals the resolution) of 10 to 15 nm. Other types of microfabricated objects, such as resolution test patterns, Zernike phase rings, uniformly redundant arrays, and the list continues to grow. Diamond's I-13 beamline is a world-class facility which can provide the highly coherent beams needed to advance the technology. Its two branches correspond to the two basic modes of imaging, in real and reciprocal space, which will provide the baseline capabilities:i) X-ray computed tomography (CT) for 3D volume imaging with amplitude or phase contrast. A rotational series of projection views is assembled into a 3D image using computation. ii) Coherent Diffraction Imaging (CDI) by phasing and subsequent inversion of diffraction patterns, either in the forward direction or around Bragg peaks from a crystalline sample. CDI, however, does require a computational phasing step, for which good algorithms are available now and better ones are under active development.On a longer time scale, the proposed methods development will interface with Diamond beamline B-24, for cryogenic Transmission X-ray Microscopy (TXM). This project needs the highest possible quality Fresnel Zone Plates operating in the water window , which could be achieved with a well-planned upgrade pathway for the Harwell microfabrication facility. Since x-ray imaging programs are totally dependent on the fabricators of these items, it is vital that routine access to the fabrication facilities should be available to UK researchers, preferably within the UK, and preferably within STFC. Having a dedicated full-time person in place working on X-ray optics within this project will be a first step in this direction.The research enabled by the new methods we will develop will see wide application in visualising the details of processes involved in biological, medical and materials science. The flexibility of the methods we will develop will also enable undertaking dynamical studies of similar processes, as well as the imaging of samples requiring sophisticated manipulation, housing and/or extreme pressure/temperature conditions. Our project has very broad scope, ranging from nanoscale structures accessible only though diffraction (CDI) to macroscale whole animal studies, necessarily requiring a large field of view. All these X-ray imaging modalities are seeing rapid growth at the present time. This project focuses on enhancements achievable by phase modulation, either by improving image contrast or by broadening the range of accessible samples by allowing them to imaged (phased) in the first place.

Planned Impact

Diamond Light Source will benefit from the development of new optics and new imaging software that is not already a part of their optics group. The international synchrotron community will benefit through publication of the new ideas and results. While I13 and B24 will benefit directly, I14, I12, I16, I07 and I22 will also feel the impact of the new techniques. The project will be carried out in close collaboration with the research interest of the I13 team (Ulrich Wagner, Zoran Pesic) and the B24 team (Liz Duke, Colin Nave). Diamond's user community will have access to new phase-sensitive imaging methods, both in real and reciprocal space, that will lead the world and give them advantages over international competition. Imaging is widely considered to be the fastest growing portion of the user community, reaching widely across the sciences from paleontology to cultural heritage. The imaging beamlines are likely to be among the most heavily sought facilities for this reason. The proposal is inherently multidisciplinary, so interactions with the other residents of RCaH will benefit from the symbiotic interactions of the results of the imaging methods to structural biology and physical science. Specifically, the membrane protein crystallography group of So Iwata and the Cryo Electron Microscopy users associated with Dave Stuart's group will see the impact. External collaborations are anticipated in the areas of industrial imaging for the coatings industry (Andrew Burgess, Akzo Nobel), and nanoparticle synthesis (Nguyen Thanh, RI). The immediate availability of imaging capabilities will undoubtably lead to the examination of entirely new kinds of materials. This work will impact the other UK funding agencies. There are already programmes funded by MRC and BBSRC in protein production and membrane protein crystallization already started in the RCaH which will be impacted by the availability of new techniques. A lively discussion has already started about ways that Protein Crystallography can be enhanced by use of coherent beams. The PI of the current proposal is finalizing details of a BBSRC funded project to study chromosome structure, for which phase modulation techniques could become a key component. Having a significant PI presence with multiple independent projects can only increase their overall impact. The developed techniques will also enable a breakthrough in fields like archeology and cultural heritage preservation in general. Currently, X-ray fluorescence is often the technique of choice for such applications; however, this normally requires scanning the samples in 2D across a pencil beam, leading to lengthy acquisitions and making 3D imaging more difficult. The imaging techniques we are proposing will provide similar levels of information in a single x-ray exposure for 2D imaging, and much faster acquisition times in 3D imaging. Interesting results have recently been obtained through phase methods on samples like ancient Chinese bronzes, relics in medieval altarpieces and specimens of early homo sapiens, and we expect that there will be much more impact from the increased sensitivity provided by the techniques we will develop. There will be impact on the Central Laser Facility, of which parts will be installed in the RCaH. To test the phasing algorithms, we will need to set up a small laser lab with a precision sample scanner. This will be able to achieve long-working-distance high resolution optical images that will be of interest to the users of the CLF. Proximity of the facilities will allow them to learn from each other. The development of a common sample mount is an obvious area of advantage to everyone.


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Description Consultant: Malcolm Howells, Lawrence Berkeley Lab Postdoc: Graeme Morrison Postdoc: Fucai Zhang

Students supported: Maria Civita, Bo Chen, Cesar Zapata, Fabio Vittoria, Henry Charlesworth, Qiaoen Luo, Ephanielle Verbanis

Our consortium was set up in the Research Complex at Harwell (RCaH) under the theme of developing phase modulation technology for X-ray imaging. This project was designed to take advantage of the I-13 Coherence and Imaging beamline at the Diamond Light Source, under construction at the time of the original proposal, which has now been in operation for about 18 months.

The main theme was originally divided into two directions: the exploitation of the phase modulation techniques themselves for phase contrast imaging and also the development of the optics themselves. The postdoc planned for the second activity (Joan Vila) decided not to join the project and Graeme Morrison took the position instead. The microfabrication facility at Harwell was also closed, so we decided instead to outsource the fabrication of test phase objects and X-ray modulators to ZonePlates Ltd. This move has been cost neutral, since a relatively large budget had been requested for the microfabrication facility access. We are happy with the service from ZonePlates Ltd and have had constructive interactions with Pambos Charalambos over the design and testing of the optics. It is also supporting the development of a UK company in a strategic field of technology.

As planned, we set up a visible light wavelength optical ptychography system in G63 of the RCaH. This was based on an Andor CMOS camera controlled by MatLab and is now in routine operation. It allows quantitative phase measurements of extended objects and has significant advantages over the classical methods of phase contrast, Schlieren, Nomarski and Zernike, which attempt to encode phase as amplitude images, but are neither quantitative nor unambiguous in their interpretation. Since the interface and control system, designed by Fucai Zhang, is user-friendly, it has been effective for student training. This has been successfully used for a number of projects to date:

i) optical "single shot" reconstructions (Fucai Zhang) ii) birefringence of growing calcite films (Henry Charlesworth) iii) ptycho-tomography of 3D refractive structures (Qiaoen Luo) iv) optical volume measurements of chromosomes (Ephanielle Verbanis) v) modal decomposition in fluctuating binary fluid mixtures (Chris Gomm) vi) cell invasion of artificial skin scaffolding substrates (Gurkeep Bhella)
Exploitation Route Interactions with other scientists in the Research Complex at Harwell. We have developed a new kind of phase contrast microscope that might see some application.
Sectors Education,Electronics,Energy,Environment,Healthcare

Description Numerous invitations to give seminars and speak at conferences. Input to science case for new facilities, such as MBA-lattice synchrotrons and XFELs.
First Year Of Impact 2012
Sector Education,Electronics,Energy,Environment,Healthcare
Impact Types Cultural,Societal,Economic

Description Chair of science advisory committee
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
Impact Facility improvement and development for benefit of users.
Description Linac Coherent Light Source, Chair of Science Advisory Committee
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Facility improvement and development for benefit of users.
Description Chair of Royal Society Conference "Real and reciprocal space X-ray imaging", 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A double event, supported as part of the Royal Society scientific meetings, was organized in February 2013 in London and at Chicheley Hall in Buckinghamshire by Dr A. Olivo and Prof. I. Robinson. The theme that joined the two events was the use of X-ray phase in novel imaging approaches, as opposed to conventional methods based on X-ray attenuation. The event in London, led by Olivo, addressed the main roadblocks that X-ray phase contrast imaging (XPCI) is encountering in terms of commercial translation, for clinical and industrial applications. The main driver behind this is the development of new approaches that enable XPCI, traditionally a synchrotron method, to be performed with conventional laboratory sources, thus opening the way to its deployment in clinics and industrial settings. The satellite meeting at Chicheley Hall, led by Robinson, focused on the new scientific developments that have recently emerged at specialized facilities such as third-generation synchrotrons and free-electron lasers, which enable the direct measurement of the phase shift induced by a sample from intensity measurements, typically in the far field. The two events were therefore highly complementary, in terms of covering both the more applied/translational and the blue-sky aspects of the use of phase in X-ray research. optics, image processing

Since Roentgen's discovery well over a century ago, X-ray imaging has been based on attenuation. While this is an effective and reliable approach, it is known to have limitations whenever objects with similar attenuation characteristics have to be distinguished, as this leads to poor image contrast. One possible solution is to generate image contrast by exploiting phase changes in the X-ray wavefront rather than attenuation: this approach is called X-ray phase contrast imaging (XPCI). Its main advantage is that the term responsible for phase effects (the unit decrement of the real part of the refractive index) is much larger than the imaginary part, responsible for attenuation. In many practical cases, this difference can be up to 1000-fold. Hence, albeit that it can be difficult to detect, phase is intrinsically a much stronger effect and can therefore lead to much higher image contrast if appropriately exploited.

The first X-ray phase contrast image dates back to 1965 and was acquired by Bonse & Hart [1] with a crystal interferometer, which has been bearing their names since. We were fortunate enough to have Prof. Hart attending our conference. Following a significant attempt by Ando & Hosoya [2] in 1972, the idea of using a crystal-based X-ray interferometer was picked up again in the 1990s, in particular by Momose's group. XPCI exploded in the mid-1990s, and, to the best of our knowledge, the first of a long series of papers published from 1995 onwards is Momose's [3], published on 1 January 1995, on results already presented in the previous year. Momose and his group continued to explore medical and biological applications of XPCI implemented with the Bonse-Hart interferometer, as reported, for example, in their 1996 Nature Medicine paper [4].

Almost simultaneously, researchers started to explore a different approach to the use of crystals in XPCI-namely the use of a perfect crystal as an 'angular analyser'. It was in fact observed that the faint distortions in the wavefront caused by phase changes translate directly into slight changes in the X-ray direction (X-ray refraction), which could therefore be picked up by a system with sufficient angular sensitivity like a perfect crystal. The fact that the refraction angle is proportional to the gradient of the phase shift gave rise to the name 'differential' XPCI, which is common to other methods listed below, such as edge-illumination and Talbot interferometry. The most famous paper pioneering this approach is the 1995 Nature letter by Davis et al. [5]. It has to be said, however, that a few known examples exist that pre-date that deservedly famous paper, where effectively the same method had been used to address specific problems, and the results were published in journals with relatively limited diffusion [6,7]. Another paper on the crystal method appeared later in the same year [8] and the method continued to be explored later, leading to some of the first simplified phase retrieval algorithms [9] and extraction of the first quantitative X-ray 'dark-field' images [10-12] (qualitative dark-field images had already been presented in [5]).

Still in 1995, a much simpler implementation, based on free-space propagation, was proposed by Snigirev et al. [13]. Through this approach, phase contrast images are acquired without the need for any additional optical element, simply by increasing the distance between sample and detector. If the source possesses enough coherence, this is sufficient to detect phase-induced interference fringes at the boundaries of the imaged objects. In the following year, Wilkins et al. [14] demonstrated that this approach works also with polychromatic radiation, something that was impossible to observe before as the use of a crystal automatically renders the beam monochromatic. Interestingly, similar images had been obtained before, but the substantially improved image contrast had not been interpreted on the basis of phase effects (e.g. [15]). Owing to its simplicity of implementation, the free-space propagation technique is still widely used, and it is the only one to date to have reached the in vivo stage for human patients [16].

A method that combines the angular selectivity principle exploited with crystal 'analysers' and the simplicity of free-space propagation, called edge-illumination XPCI, was developed in the late 1990s [17]. As the name suggests, it performs a fine selection on X-ray direction by illuminating only the physical edge of the detector pixels, and by doing so it eliminates the need for a perfect crystal, opening the way to polychromatic and divergent X-ray beams. This was later exploited to adapt the method for use with conventional X-ray sources [18], which also led to the first quantitative phase retrieval performed with incoherent illumination of the sample [19].

In the early 2000s, a further approach was introduced, based on the adaptation to X-rays of Talbot and Talbot-Lau interferometers, well-known methods among the optics community. This adaptation was made possible by novel nanofabrication techniques, which enabled the development of gratings with a pitch sufficiently small to produce Talbot 'self-images' [20] at X-ray wavelengths when coherently illuminated. The approach was first demonstrated in the 'Talbot' set-up by David et al. [21] and by Momose's group shortly afterwards [22]; a few years later, Pfeiffer et al. [23] demonstrated that the Talbot-Lau arrangement could also be implemented with X-rays, opening the way to the use of laboratory sources. In a further study, it was shown that the same set-up could also be used to obtain quantitative dark-field images [24], along the lines of what was previously done with analyser crystals [10-12]. To extract phase and dark-field signals, a technique called phase stepping is employed, in which one of the two (Talbot) or three (Talbot-Lau) gratings is scanned with respect to the others, and individual images are acquired at each scanning position. Later on, Wen et al. [25] developed a similar approach, which, however, employed a single grating, and, instead of using a phase-stepping method to isolate the different signals, did so by applying a Fourier-based analysis method to a single frame.

Quite remarkably, most of the leading figures behind the above developments agreed to participate in the conference, which meant that most of the above topics were covered in the various talks. Another interesting aspect that emerged is that the field is continuing to evolve, with new examples of implementation already being presented at this same meeting (e.g. Wen et al. [26] realized gratings with nanometric pitch which led to a hybrid between Talbot and Bonse-Hart interferometry), new implementation schemes (e.g. [27]), use of materials as common as paper to replace gratings or analysers [28] and much more. This extreme liveliness indicates a prosperous future for the area, both in terms of new methods and new applications, and definitely looks encouraging in terms of ultimately reaching the 'translation into mainstream application' goal which inspired this meeting.
Year(s) Of Engagement Activity 2013
Description Invited talks at conferences: 20 per year 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invitation accepted to travel to international conference, give invited talk and discuss with participants at length.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017
Description Size Strain conference, chair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Beams of penetrating radiation, such as X-ray photons, neutrons and electrons, provide the basis for a whole host of tools for probing material structure, composition and properties. In particular, over a century of using reciprocal space methods based on diffraction has allowed reveal- ing intricate details of complex molecules, collecting multi-scale infor- mation about different levels of structural organization, observing the course of reactions and processes, etc.
Although methods and approaches in this field are well-established, the proliferation of hardware and software tools in the recent years has led to a considerable increase in the ease of access to many techniques. This increases their attractiveness for the community, and an ever great- er number of researchers make use of large scale facilities and advanced instruments.
The 7th Size-Strain conference 'Diffraction Analysis of the Microstruc- ture of Materials' (SS-VII) was held at Oxford from 21 to 24 September 2015. The 80 participants were able to enjoy four days of college living at Trinity College, whilst all plenary conference sessions were held at the nearby Department of Engineering Science of the University of Oxford. On the final day of the conference, a half-day trip was arranged to the large scale facilities at the nearby Harwell campus, Diamond Light Source (DLS), the UK synchrotron, and ISIS neutron spallation source. The conference planning, booking and logistics were run extremely smoothly and efficiently by the DLS events team. The meeting was co- chaired by Ian Robinson (University College London) and Alexander Korsunsky (University of Oxford).
The scientific programme of the conference continued the themes set and addressed at the previous meetings in Garmisch-Partenkirchen (SS- V) and Giens (SS-VI). These address the investigation of material micro- structure and properties by diffraction methods, with a special interest in their application to polycrystalline materials, the methodologies for the study of lattice defects, residual stress and texture in thin films, nano- structures and at surfaces, line-broadening analysis, line-profile fitting, and modelling based on the fundamental parameters. In addition to the new and by now well-established topics of microbeam diffraction and co- herent diffraction introduced at SS-VI, the SS-VII saw the addition of X-ray and neutron imaging and Pair Distribution Function (PDF) analysis.
The conference was opened with an inspiring plenary talk by Cev Noyan (Columbia Uuniversity) entitled "The Anatomy of a Powder Dif- fraction Experiment", which prompted a lively discussion and set the mood for open and active exchange of views, experiences and ideas. Further invited presentations were given by Clare Grey (Cambridge) on "X-ray Diffraction Methods for Studying Structure and Dynamics in Batteries and Supercapacitors", Thomas Hansen (ILL) on "Stacking faults in ice", Felix Hofmann (Oxford) on "Probing Atomic Scale Defects", Alberto Leonardi (Indiana) on "Microstrain in nanomaterials: XRD line profile interpretation enhanced by Molecular Dynamics simulations",
0264-1275/© 2016 Elsevier Ltd. All rights reserved.
Reinhard Neder (Erlangen) on "Size and strain analysis of small highly disordered nanoparticles" and by Tobias Schulli (ESRF) on "The nanodiffraction Beamline ID01/ESRF: diffraction microscopy and coherent diffraction imaging for high resolution structural analysis". Instead of split- ting the conference into parallel sessions, the chairs took the decision to treat all participants to the opportunity to obtain a complete view of the research landscape in the field by attending all focused sessions on the key topics, including Disorder, Defects, Morphology, Nanoscience, Thin Films, Alloys, Oxides, Strain Mapping, Dynamics, and 3D Imaging.
The Virtual Special Issue of Materials and Design captures some of the interesting work presented at the conference in the form of con- tributed full length articles. Particular care has been taken by the ed- itorial team to ensure that the publications were in line with the journal scope and editorial preferences described in the editorial note [1]. This Virtual Special Issue demonstrated the wide variety of applications of advanced diffraction methodologies in modern materials science. The full details of published articles can be found at the VSI web page: 10ZD8MPKNFV.
The Special Issue Guest Editors express sincere appreciation to all authors and reviewers for their dedication in putting together a high quality body of joint work. Our gratitude is also due to the Materials & Design editorial team and technical staff for their cooperation and excel- lent service. Financial support from Diamond Light Source towards run- ning Size-Strain VII is gratefully acknowledged, as are the contributions to event organization from Zoe Cattell and Sarah Bucknall (DLS), and Eva Williams (Engineering Science). Particular thanks are due to Kevin Knott CVO, Estates Bursar of Trinity College, for the permission to use college facilities.
[1] A.M. Korsunsky, A.G. Gibson, G.D. Nguyen, M. Sebastiani, X. Song, T. Sui, Editorial note - on the aims & scope and priority areas in Materials & Design, Mater. Des. 88 (2015) 1377-1380.
Ian Robinson is group leader in the Condensed Matter Physics and Materials Science De- partment at Brookhaven National Laboratory, and Professor at the London Centre for Nanotechnology, University College. His research is currently focused on the development of coherent X-ray diffraction methods for image the structure of nanoparticles. His re- search makes extensive use of synchrotron radiation and Free Electron Lasers. He built a beamline at Brookhaven to develop Surface X-ray Diffraction and a second one at Argonne for Coherent X-ray Diffraction. One outcome of the work was the discovery of Crystal Truncation Rods, for which he was awarded the Surface Structure Prize in 2011 and the Gregori Aminoff Prize in 2015.
Year(s) Of Engagement Activity 2015