Understanding the functional makeup of the brain is a holy grail of neuroscience, and imaging tools play a significant role in achieve this aim. Functional imaging is a more difficult goal than anatomical imaging because it depends on establishing a contrast mechanism that relates to physiological function and also can be measured with good accuracy and resolution. Optical techniques are very attractive because of the rich information encoded in the absorption spectra of many different molecules, but they are difficult to use at large scale because of the high degree of scattering that occurs in passing through different tissues of the body. By using time-resolved measurements of the propagation of light from multiple illumination patterns, diffuse optical tomography (DOT) can produced low-resolution images of absorption and scattering properties, and decorrelate these to produce maps of oxygenation in the brain and other organs. At the same time, diffuse correlation spectroscopy (DCS) examines the way in which coherent light is decorrelated from itself when compared over time. This decorrelation naturally occurs due to the Brownian motion of endogenous scattering particles, and blood flow. Coherent optical techniques thus allow the non-invasive monitoring of blood flow and provide an indication of pathological cerebral auto-regulation during, e.g., stroke. Until recently, limitations in coherent detection technology have prevented significant developments towards diffuse correlation tomography (DCT), wherein volumetric images of blood flow can be produced. In this project we aim to develop a system for DCT and time-resolved DOT in one device. This will bring the two techniques together to provide images of cerebral blood flow and cerebral metabolic rate of oxygen extraction in the brain for the first time. We propose the development of theoretical and experimental methods which will enable the development of a new generation of optical instruments for portable, low-cost, continuous simultaneous monitoring of blood flow and chromophore concentrations. The rich images produced by our system have the potential to vastly improve our understanding of underlying neurological processes and pathology, and to allow the efficient use of scarce resources in targeted treatments.

How can we make a movie of atoms - or even electrons - moving inside molecules? This is a fundamental problem in many fields of physics, chemistry and biology. For this, we need pulses of light with a duration which is much shorter than the characteristic times of the movements of the atoms or electrons. For the case of atoms this is typically a few femtoseconds (1fs is one billionth of a nanosecond); electrons move even faster, on the attosecond scale, where (1 attosecond is one thousandth of a femtosecond!). We also need very short wavelengths, such as those of X-rays, so to achieve the necessary resolution at the nanometre scale. Meeting these requirements is a formidable challenge, but the pay-off in terms of applications, ranging to medical science to material engineering, is enormous. Cutting-edge imaging experiments of this type have already been achieved by using X-ray sources in huge facilities. However, their large scale and operating cost prevents them from becoming a widespread tool. There is a more convenient and compact way of producing very short X-ray pulses. If we shine short pulses of visible light on a jet of gas, such as argon, the atoms of the gas respond to the presence of this light by emitting bursts of extreme ultraviolet and soft X-ray radiation by a process called "high harmonic generation" (HHG). The applicability of these pulses for probing electronic dynamics in atoms and molecules has been tested in a series of pioneering experiments. However, the brightness of HHG sources is far from being comparable with that of large-scale facilities. We will investigate the prospects for making HHG a fully viable technique for taking "molecular movies" with a system small enough for an ordinary R&D laboratory. We have identified solutions for overcoming current limitations: in particular, we will work on choosing the best possible visible light for producing HHG radiation, as well as on employing techniques of "phase-matching", i.e. controlling how the light propagates through the jet, to increase the efficiency of generation. HHG beams are akin to an X-ray laser, with which they share properties of coherence. This implies that, if we collect the full information on the amplitude and the phase of the light far from our target, we can use sophisticated computer codes to reconstruct the shape of this object. This avoids using lenses for X-rays, which are difficult to manufacture. Further, by tuning the wavelength of the X-ray beam it is possible to select and image only a specified atomic element in the object. We will demonstrate the utility of the bright HHG beams we plan to develop in proof-of-principle experiments on aluminium alloys. These alloys - which are of crucial importance to the aerospace, automotive, and electronic industries - derive their strength from the formation of inhomogeneities during heat treatment. However, the relation between their microscopic structure and mechanical properties is not well understood; our demonstration experiments may open a new route for exploring these important issues. From a fundamental viewpoint, the electromagnetic field contains the maximum possible information about an object that can be obtained in an optical experiment. Hence we will also investigate methods able fully to characterize the X-ray field scattered from an object, allowing the spatial and structural dynamics of the object to be tracked. In summary, we plan to take major steps towards laboratory-scale imaging at atomic spatial and temporal scales by developing bright, compact pulsed soft-X-ray sources and measurement methods that return the full details of the radiation field incident on, and scattered from, the object under study. This research programme therefore has the potential to deliver a step change in what is possible in spatio-temporal imaging at the nanoscale

Two-dimensional materials (2DM), derived from bulk layered crystals with covalent intra-layer bonding and weak van der Waals (vdW) interlayer coupling, offer a versatile playground for creating quantum materials with properties tailored for particular applications. This is achieved by combining different atomically thin 2DM crystals into heterostructures layer-by-layer in a chosen sequence. Unlike conventional crystal growth, this technique is not limited by lattice matching or interface chemistry, hence, it enables us to build heterostructures from several dozens of readily available vdW crystals with diverse physical properties (electronic, optical or magnetic). This platform offers broadly acknowledged potential for the realisation of nano-devices and designer meta-materials with new properties and functionalities determined by the coupling of adjacent layers, including interlayer band hybridisation and strong proximity effects. A new degree of freedom for controlling the properties of vdW heterostructures is the mutual crystal rotation - twist - of the constituent 2D crystals. Together with the lattice mismatch of the adjacent 2D crystals it gives rise to the moiré superlattice (mSL): a periodic variation of the local atomic registry, with the period controlled by the twist angle. Even a small twist can lead to remarkable changes in the properties of heterostructures - for instance, in homobilayers of 2DM it leads to strong spectrum reconstruction and formation of electron and hole minibands. So far, the breakthrough studies of moiré superlattices have been focused on graphene heterostructures with hexagonal boron nitride and on twisted graphene bilayers. Recently, initial exploration of twisted layers of transition metal dichalcogenides have begun, featuring four letters in a single issue of Nature in March 2019 (in one of those the members of this consortium have reported moire minibands for excitons). Not surprisingly, these recent developments have fuelled a world-wide race to develop this new field of materials science and solid state physics, branded as 'twistronics'. This project will pioneer the new scientific area of twistronics in novel types of 2DM heterostructures, mapping out the limits to which one can control their properties through the interlayer proximity and moiré superlattice effects. Using this approach, we aim to engineer flat electronic bands in semiconducting 2DM heterostructures, promoting quantum many-body effects, which we will explore through quantum transport and optical studies. Furthermore, we will realise the world-first twisted bilayers of new emerging 2DMs that exhibit strongly correlated states in their natural form ((anti)ferromagnetic, charge-density waves, or superconductivity) and explore novel physics in those system with an outlook for practical applications. In all material combinations, we will look into two distinct cases of (1) intermediate twist angles, where lattices are expected to behave as rigid solids, producing smooth variation in interlayer registry and (2) small twist angles where we have recently found that twisted 2D materials reconstruct to form extended commensurate domains separated by stacking faults. To achieve the ambitious and game-changing goals of this proposal, the consortium will employ a recently commissioned world-first nanofabrication facility, which allows assembly of van der Waals heterostructures in ultra-high vacuum. This unique instrument will provide the game-changing quality materials necessary for this project. Funding of this proposal will allow us to fully employ the potential of this new instrument and deliver ground-breaking new research and disruptive technologies.