A Macroscopically Relevant 3D‐Metrology Approach for Nanocatalysis Research

A 3D nanometrological approach, which considers as an unbiased validation criterion the quantitative match between values of properties determined by macroscopic characterization techniques and those determined from the nanoscopic results, is developed to unveil the details of complex nanocatalysts. This approach takes into account both the peculiar characteristics of this type of materials and the large influence of noise in the tilt series. It combines, in an optimized way, the latest experimental developments in high angle annular dark field scanning transmission electron microscopy mode (HAADF‐STEM) tomography, such as batch tomography, image denoising by undecimated wavelet transforms, improved reconstructions by total variation minimization and a more efficient, user‐independent, segmentation scheme. To illustrate the use of this novel approach, the 3D structural characterization of a model nanocatalyst comprising gold nanoparticles dispersed on the surface of CeO₂ nanocubes is performed, and the obtained results used to compute the values of different macroscopic chemical and textural properties. Comparison with values obtained by macroscopic characterization techniques match very closely those obtained by 3D nanometrology. Importantly, the new approach described in this work also illustrates a pipeline for nearly fully automated HAADF‐STEM tomography studies, guaranteeing reliable correlations between nanoscopic and macroscopic properties.     

Sharp estimate of electric field from a conductive rod and application

We are concerned with the quantitative study of the electric field perturbation due to the presence of an inhomogeneous conductive rod embedded in a homogenous conductivity. We sharply quantify the dependence of the perturbed electric field on the geometry of the conductive rod. In particular, we accurately characterize the localization of the gradient field (i.e., the electric current) near the boundary of the rod where the curvature is sufficiently large. We develop layer‐potential techniques in deriving the quantitative estimates and the major difficulty comes from the anisotropic geometry of the rod. The result complements and sharpens several existing studies in the literature. It also generates an interesting application in EIT (electrical impedance tomography) in determining the conductive rod by a single measurement, which is also known as the Calderón's inverse inclusion problem in the literature.     

Modal decomposition from partial measurements

A data set over space and time is assumed to have a low-rank representation in separated spatial and temporal modes. The problem of evaluating these modes from a temporal series of partial measurements is considered. Each elementary instantaneous measurement captures only a “window” (in space) of the observed data set, but the position of this window varies in time so as to cover the entire region of interest and would allow for a complete measurement would the scene be static. A novel procedure, alternative to the Gappy Proper Orthogonal Decomposition (GPOD) methodology, is introduced. It is a fixed-point iterative procedure where modes are evaluated sequentially. Tested upon very sparse acquisition (1% of measurements being available) and very noisy synthetic data sets (10% noise), the proposed algorithm is shown to outperform two variants of the GPOD algorithm, with much faster convergence, and better reconstruction of the entire data set.     

Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18F-Labeled PSMA-Tracers for Prostate Cancer Imaging

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t_1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [⁶⁸Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.     

Monte Carlo simulations of an innovative molecular breast imaging system for the small breast cancer diagnosis using GATE

ABSTRACT

This paper draws attention to the study of performance of a new Molecular Breast Imaging (MBI) device, whose purpose is the early diagnosis of breast cancer, using Monte Carlo simulations. MBI provides functional and specific information that are more appropriated to dense breasts. Two asymmetric heads with different types of collimators, facing each other in anti-parallel viewing direction, characterize the system. Detectors and phantoms, together with the data taking procedure, are shortly reported. Monte Carlo simulations using the GATE (GEANT4 Application for Tomographic Emission) simulation toolkit have been implemented to evaluate the optimal detector configuration, in terms of sensitivity and spatial resolution, and also to reproduce the real experimental data. The device can be used both in spot compression and in Limited Angle Tomography (LAT); in the latter configuration one detector head with pinhole collimator is able to rotate around the breast in order to diagnose and localized the small tumors.     

Atomic‐Scale Mapping of Impurities in Partially Reduced Hollow TiO2 Nanowires

The incorporation of impurities during the chemical synthesis of nanomaterials is usually uncontrolled and rarely reported because of the formidable challenge in measuring trace amounts of often light elements with sub‐nanometer spatial resolution. And yet, these foreign elements (introduced by doping, for example) influence functional properties. We demonstrate how the hydrothermal growth and a partial reduction reaction on hollow TiO₂ nanowires leads to the introduction of parts per millions of boron, sodium, and nitrogen. This doping explains the presence of oxygen vacancies and reduced Ti states at the surface, which enhance the functional properties of TiO₂. Our results were obtained on model metal oxide nanomaterials and they shed light on a general process that leads to the uncontrolled incorporation of trace impurities in TiO₂, thereby, having a strong effect on applications in energy‐harvesting.     

An Unsymmetrical Squaraine-Based Activatable Probe for Imaging Lymphatic Metastasis by Responding to Tumor Hypoxia with MSOT and Aggregation-Enhanced Fluorescent Imaging

Optoacoustic imaging has great potential for preclinical research and clinical practice, and designing robust activatable optoacoustic probes for specific diseases is beneficial for its further development. Herein, an activatable probe has been developed for tumor hypoxia imaging. For this probe, indole and quinoline were linked on each side of an oxocyclobutenolate core to form an unsymmetrical squaraine. A triarylamine group was incorporated to endow the molecule with the aggregation enhanced emission (AEE) properties. In aqueous media, the squaraine chromophore aggregates into the nanoprobe, which specifically responds to nitroreductase and produces strong optoacoustic signals due to its high extinction coefficient, as well as prominent fluorescence emission as a result of its AEE feature. The nanoprobe was used to image tumor metastasis via the lymphatic system both optoacoustically and fluorescently. Moreover, both the fluorescence signals and three-dimensional multispectral optoacoustic tomography signals from the activated nanoprobe allow us to locate the tumor site and to map the metastatic route.     

Lipophilicity data for some preservatives estimated by reversed-phase liquid chromatography and different computation methods

The chromatographic behavior of some preservatives was performed by reversed-phase high-performance liquid chromatography on C18 (LiChroCART, Purosphere RP-18e), C8 (Zorbax, Eclipse XDB-C8), CN100 (Säulentechnik, Lichrosphere) and NH₂ (Supelcosil LC-NH₂) columns. The lipophilicity estimated for the first time on the first three columns are comparable and very well correlated. The mobile phase was a mixture of methanol–water (0.1% formic acid) in different volume proportions from 40% to 60% (v/v) for RP-C18, RP-C8 and RP-CN100 column (exception for parabens on RP-C8 column—the methanol concentrations being from 55% to 65%) and from 30% to 50% (v/v) for RP-NH₂. Highly significant correlations were obtained between different experimental indices of lipophilicity (log k_w, S, φ₀, mean of k and log k, and scores of k and log k corresponding to the first principal component) and computed log P values, and C8 column seems to be more suited for estimating the lipophilicity of the investigated compounds. These direct correlations offer a very good opportunity to derive powerful predictive models via Collander-type equations. The reliability of scores values as lipophilic indices is shown by their high correlation with the log K_ow obtained using classical “shake-flask” technique, log k_w and also some of the computed log P values. In addition, the results obtained applying PCA to the retention data may be used in interpreting the molecular mechanism of interactions between eluents and stationary phases with different polarity and to explain the chromatographic behavior of compounds. Finally, the “congeneric lipophilicity chart” described by the scores corresponding to the first principal component has the effect of separating compounds from each other more effectively from congeneric ((dis)similarity) point of view. The parabens and tert-butylhydroquinone appeared to be the most lipophilic preservatives.