Probing the Boundary between Classical and Quantum Mechanics by Analyzing the Energy Dependence of Single-Electron Scattering Events at the Nanoscale.

The relation between the energy-dependent particle and wave descriptions of electron-matter interactions on the nanoscale was analyzed by measuring the delocalization of an evanescent field from energy-filtered amplitude images of sample/vacuum interfaces with a special aberration-corrected electron microscope. The spatial field extension coincided with the energy-dependent self-coherence length of propagating wave packets that obeyed the time-dependent Schrödinger equation, and underwent a Goos-Hänchen shift. The findings support the view that wave packets are created by self-interferences during coherent-inelastic Coulomb interactions with a decoherence phase close to Δφ = 0.5 rad. Due to a strictly reciprocal dependence on energy, the wave packets shrink below atomic dimensions for electron energy losses beyond 1000 eV, and thus appear particle-like. Consequently, our observations inevitably include pulse-like wave propagations that stimulate structural dynamics in nanomaterials at any electron energy loss, which can be exploited to unravel time-dependent structure-function relationships on the nanoscale.

Wave-like calcification on the posterior surface of an acrylic hydrophilic bag-in-the-lens (BIL) implant.

Purpose: To report secondary opacification of a hydrophilic bag-in-the-lens (BIL) which is a rare manifestation that can happen years after initial surgery. Observations: We describe a case of a prominent wave-like, rippled opacification on the posterior surface of the BIL. The opacification was composed of calcium deposits and seems to start in the periphery as a ring and progresses to the centre of the posterior surface. Due to the specific design of the BIL, there is direct contact between the BIL and the posterior chamber, both with the space of Berger, and the anterior hyaloid, particularly in this very hyperopic eye. Conclusions and importance: Abnormal fluid flow and stagnation in an unusual retrolenticular space is a possible explanation for this unusual pattern of posterior surface opacification.

Probing atom dynamics of excited Co-Mo-S nanocrystals in 3D.

Advances in electron microscopy have enabled visualizations of the three-dimensional (3D) atom arrangements in nano-scale objects. The observations are, however, prone to electron-beam-induced object alterations, so tracking of single atoms in space and time becomes key to unravel inherent structures and properties. Here, we introduce an analytical approach to quantitatively account for atom dynamics in 3D atomic-resolution imaging. The approach is showcased for a Co-Mo-S nanocrystal by analysis of time-resolved in-line holograms achieving ~1.5 Å resolution in 3D. The analysis reveals a decay of phase image contrast towards the nanocrystal edges and meta-stable edge motifs with crystallographic dependence. These findings are explained by beam-stimulated vibrations that exceed Debye-Waller factors and cause chemical transformations at catalytically relevant edges. This ability to simultaneously probe atom vibrations and displacements enables a recovery of the pristine Co-Mo-S structure and establishes, in turn, a foundation to understand heterogeneous chemical functionality of nanostructures, surfaces and molecules.

Snapshot 3D Electron Imaging of Structural Dynamics.

In order to understand the physical properties of materials it is necessary to determine the 3D positions of all atoms. There has been significant progress towards this goal using electron tomography. However, this method requires a relatively high electron dose and often extended acquisition times which precludes the study of structural dynamics such as defect formation and evolution. In this work we describe a method that enables the determination of 3D atomic positions with high precision from single high resolution electron microscopic images of graphene that show dynamic processes. We have applied this to the study of electron beam induced defect coalescence and to long range rippling in graphene. The latter strongly influences the mechanical and electronic properties of this material that are important for possible future applications.

Imaging theory for the ISTEM imaging mode.

A relatively simple yet accurate analytical model for the image formation in the imaging scanning TEM (ISTEM) imaging mode, which implements partial spatial incoherence using a combination of scanning illumination and conventional imaging, is presented. Based on an object function approximation the ISTEM intensity can be divided into a constant, a linear and a nonlinear term. Under certain conditions, which are discussed, the formation of both linear and nonlinear terms can be expressed by convolutions with point spread functions. A closer inspection of these allows an insight into the advantages of ISTEM compared to conventional TEM (CTEM). The findings of the proposed model are confirmed by comparison to multislice simulations. A close investigation of the linear coherent contrast transfer function allows the derivation of optimal imaging conditions to reach a maximum resolution for a given signal-to-noise ratio. The robustness of ISTEM towards temporal incoherence is finally demonstrated and discussed within the model.

Hollow Cone Electron Imaging for Single Particle 3D Reconstruction of Proteins.

The main bottlenecks for high-resolution biological imaging in electron microscopy are radiation sensitivity and low contrast. The phase contrast at low spatial frequencies can be enhanced by using a large defocus but this strongly reduces the resolution. Recently, phase plates have been developed to enhance the contrast at small defocus but electrical charging remains a problem. Single particle cryo-electron microscopy is mostly used to minimize the radiation damage and to enhance the resolution of the 3D reconstructions but it requires averaging images of a massive number of individual particles. Here we present a new route to achieve the same goals by hollow cone dark field imaging using thermal diffuse scattered electrons giving about a 4 times contrast increase as compared to bright field imaging. We demonstrate the 3D reconstruction of a stained GroEL particle can yield about 13.5 Å resolution but using a strongly reduced number of images.

Advanced electron crystallography through model-based imaging.

The increasing need for precise determination of the atomic arrangement of non-periodic structures in materials design and the control of nanostructures explains the growing interest in quantitative transmission electron microscopy. The aim is to extract precise and accurate numbers for unknown structure parameters including atomic positions, chemical concentrations and atomic numbers. For this purpose, statistical parameter estimation theory has been shown to provide reliable results. In this theory, observations are considered purely as data planes, from which structure parameters have to be determined using a parametric model describing the images. As such, the positions of atom columns can be measured with a precision of the order of a few picometres, even though the resolution of the electron microscope is still one or two orders of magnitude larger. Moreover, small differences in average atomic number, which cannot be distinguished visually, can be quantified using high-angle annular dark-field scanning transmission electron microscopy images. In addition, this theory allows one to measure compositional changes at interfaces, to count atoms with single-atom sensitivity, and to reconstruct atomic structures in three dimensions. This feature article brings the reader up to date, summarizing the underlying theory and highlighting some of the recent applications of quantitative model-based transmisson electron microscopy.

Do you believe that atoms stay in place when you observe them in HREM?

Recent advancements in aberration-corrected electron microscopy allow for an evaluation of unexpectedly large atom displacements beyond a resolution limit of ∼0.5 Å, which are found to be dose-rate dependent in high resolution images. In this paper we outline a consistent description of the electron scattering process, which explains these unexpected phenomena. Our approach links thermal diffuse scattering to electron beam-induced object excitation and relaxation processes, which strongly contribute to the image formation process. The effect can provide an explanation for the well-known contrast mismatch ("Stobbs factor") between image calculations and experiments.

Fe-vacancy order and superconductivity in tetragonal ß-Fe1-xSe.

Several superconducting transition temperatures in the range of 30-46 K were reported in the recently discovered intercalated FeSe system (A1-xFe2-ySe2, A = K, Rb, Cs, Tl). Although the superconducting phases were not yet conclusively decided, more than one magnetic phase with particular orders of iron vacancy and/or potassium vacancy were identified, and some were argued to be the parent phase. Here we show the discovery of the presence and ordering of iron vacancy in nonintercalated FeSe (PbO-type tetragonal ß-Fe1-xSe). Three types of iron-vacancy order were found through analytical electron microscopy, and one was identified to be nonsuperconducting and magnetic at low temperature. This discovery suggests that the rich-phases found in A1-xFe2-ySe2 are not exclusive in Fe-Se and related superconductors. In addition, the magnetic ß-Fe1-xSe phases with particular iron-vacancy orders are more likely to be the parent phase of the FeSe superconducting system instead of the previously assigned ß-Fe1+δTe.

Advanced electron microscopy for advanced materials.

The idea of this Review is to introduce newly developed possibilities of advanced electron microscopy to the materials science community. Over the last decade, electron microscopy has evolved into a full analytical tool, able to provide atomic scale information on the position, nature, and even the valency atoms. This information is classically obtained in two dimensions (2D), but can now also be obtained in 3D. We show examples of applications in the field of nanoparticles and interfaces.

'Big Bang' tomography as a new route to atomic-resolution electron tomography.

Until now it has not been possible to image at atomic resolution using classical electron tomographic methods, except when the target is a perfectly crystalline nano-object imaged along a few zone axes. The main reasons are that mechanical tilting in an electron microscope with sub-ångström precision over a very large angular range is difficult, that many real-life objects such as dielectric layers in microelectronic devices impose geometrical constraints and that many radiation-sensitive objects such as proteins limit the total electron dose. Hence, there is a need for a new tomographic scheme that is able to deduce three-dimensional information from only one or a few projections. Here we present an electron tomographic method that can be used to determine, from only one viewing direction and with sub-ångström precision, both the position of individual atoms in the plane of observation and their vertical position. The concept is based on the fact that an experimentally reconstructed exit wave consists of the superposition of the spherical waves that have been scattered by the individual atoms of the object. Furthermore, the phase of a Fourier component of a spherical wave increases with the distance of propagation at a known 'phase speed'. If we assume that an atom is a point-like object, the relationship between the phase and the phase speed of each Fourier component is linear, and the distance between the atom and the plane of observation can therefore be determined by linear fitting. This picture has similarities with Big Bang cosmology, in which the Universe expands from a point-like origin such that the distance of any galaxy from the origin is linearly proportional to the speed at which it moves away from the origin (Hubble expansion). The proof of concept of the method has been demonstrated experimentally for graphene with a two-layer structure and it will work optimally for similar layered materials, such as boron nitride and molybdenum disulphide.

Applying an information transmission approach to extract valence electron information from reconstructed exit waves.

The knowledge of the valence electron distribution is essential for understanding the properties of materials. However this information is difficult to obtain from HREM images because it is easily obscured by the large scattering contribution of core electrons and by the strong dynamical scattering process. In order to develop a sensitive method to extract the information of valence electrons, we have used an information transmission approach to describe the electron interaction with the object. The scattered electron wave is decomposed in a set of basic functions, which are the eigen functions of the Hamiltonian of the projected electrostatic object potential. Each basic function behaves as a communication channel that transfers the information of the object with its own transmission characteristic. By properly combining the components of the different channels, it is possible to design a scheme to extract the information of valence electron distribution from a series of exit waves. The method is described theoretically and demonstrated by means of computer simulations.

Machine learning study of several classifiers trained with texture analysis features to differentiate benign from malignant soft-tissue tumors in T1-MRI images.

PURPOSE: To study, from a machine learning perspective, the performance of several machine learning classifiers that use texture analysis features extracted from soft-tissue tumors in nonenhanced T1-MRI images to discriminate between malignant and benign tumors. MATERIALS AND METHODS: Texture analysis features were extracted from the tumor regions from T1-MRI images of clinically proven cases of 49 malignant and 86 benign soft-tissue tumors. Three conventional machine learning classifiers were trained and tested. The best classifier was compared to the radiologists by means of the McNemar's statistical test. RESULTS: The SVM classifier performs better than the neural network and the C4.5 decision tree based on the analysis of their receiver operating curves (ROC) and cost curves. The classification accuracy of the SVM, which was 93% (91% specificity; 94% sensitivity), was better than the radiologist classification accuracy of 90% (92% specificity; 81% sensitivity). CONCLUSION: Machine learning classifiers trained with texture analysis features are potentially valuable for detecting malignant tumors in T1-MRI images. Analysis of the learning curves of the classifiers showed that a training data size smaller than 100 T1-MRI images is sufficient to train a machine learning classifier that performs as well as expert radiologists.

A fast reciprocal space method for image simulation.

In this paper, we introduce a fast reciprocal space method for image simulation. It is well known that the scattering matrix (SM) P with NxN elements consists of N different structure factors and N different excitation errors. However, most structure factors of the SM P are extremely small so that they can be neglected. Therefore, the size of the SM P is reduced drastically. On the other hand, the structure factors have two-dimensional space group symmetries, so that by reducing the symmetry related structure factors to symmetrically independent structure factors, the size of the SM P can be reduced further. The calculation speed based on the simplified SM P will be several hundred times faster than that by other conventional methods. In this paper, we describe the method for how to reduce the SM P in detail and give an example of implementation.

Clinical comparison of 6 aberrometers. Part 2: statistical comparison in a test group.

PURPOSE: To compare and mutually validate the measurements of 6 aberrometers: the Visual Function Analyzer (Tracey), the OPD-Scan (ARK-10000, Nidek), the Zywave (Bausch & Lomb), the WASCA (Carl Zeiss Meditec), the MultiSpot Hartmann-Shack device, and the Allegretto Wave Analyzer. SETTING: University Hospital Antwerp, Antwerp, Belgium. METHODS: This prospective study was conducted on a group of 44 healthy eyes with refractions ranging from -5.25 diopters (D) to +5.25 D (cylinder 0 to -2 D). For each aberrometer and each eye, the averaged Zernike data were used to calculate various kinds of root-mean-square (RMS). These parameters, together with the refractive parameters, were then analyzed with a repeated-measures analysis of variance (ANOVA) test, complemented by paired t tests. A similar analysis was done for the comparison of the variances of these parameters. RESULTS: The aberrometers gave comparable values for all studied parameters with the following exceptions: The OPD-Scan underestimated the polynomials describing 4- and 5-fold symmetries, and the Visual Function Analyzer slightly overestimated the astigmatism terms. The 3rd-order radial RMS value was different for each device, as well as the RMS in the central 2.0 mm zone. The WASCA presented the lowest variance. CONCLUSION: These results suggest that in healthy eyes, all aberrometers produced globally similar results but they may vary in some details.

Resolution of coherent and incoherent imaging systems reconsidered - Classical criteria and a statistical alternative.

The resolution of coherent and incoherent imaging systems is usually evaluated in terms of classical resolution criteria, such as Rayleigh's. Based on these criteria, incoherent imaging is generally concluded to be 'better' than coherent imaging. However, this paper reveals some misconceptions in the application of the classical criteria, which may lead to wrong conclusions. Furthermore, it is shown that classical resolution criteria are no longer appropriate if images are interpreted quantitatively instead of qualitatively. Then one needs an alternative criterion to compare coherent and incoherent imaging systems objectively. Such a criterion, which relates resolution to statistical measurement precision, is proposed in this paper. It is applied in the field of electron microscopy, where the question whether coherent high resolution transmission electron microscopy (HRTEM) or incoherent annular dark field scanning transmission electron microscopy (ADF STEM) is preferable has been an issue of considerable debate.

Clinical comparison of 6 aberrometers. Part 1: Technical specifications.

PURPOSE: To provide a detailed assessment of the techniques, technical features, and practical use of 6 aberrometers made available to our institution from September 2002 to January 2004. SETTING: Department of Ophthalmology, University Hospital Antwerp, Antwerp, Belgium. METHODS: A number of technical and practical parameters are listed for the Visual Function Analyzer (Tracey), the OPD-scan (ARK 10000; Nidek), the Zywave (Bausch & Lomb), the WASCA (Carl Zeiss Meditec), the MultiSpot Hartmann-Shack device, and the Allegretto Wave Analyzer including working principles, data acquisition, aberrometer alignment, wavefront calculation, and data analysis. Operator and patient comfort as well as practical advantages and disadvantages are discussed. CONCLUSION: All devices met at least half the following parameters: alignment, correction for source wavelength, data averaging, measurement quality check, and inhibition of accommodation.

High-resolution X-ray microtomography for the detection of lung tumors in living mice.

In the present study, the feasibility of applying high-resolution microtomography (micro-CT) for the detection of lung tumors was investigated in live mice at an early and more advanced stage of tumor development. The chest area of anesthesized mice was scanned by X-ray micro-CT. In mice with a minor and heavy tumor load, micro-CT proved to be a fast and noninvasive imaging device for the detection of lung tumors. After validation of the CT data by histologic sectioning, it was shown that the majority of tumors could be distinguished in the reconstructed virtual slices obtained by micro-CT. The data from micro-CT were also confirmed by visual inspection of the inflated and excised lungs postmortem. In vivo micro-CT opens broad perspectives for imaging tumor development and its progression in a noninvasive way. Micro-CT also allows for longitudinal evaluation of the treatment of lung cancer by drugs.