Exoscope-based videocapillaroscopy system for in vivo skin microcirculation imaging of various body areas.

The capillary system immediately responds to many pathologies and environmental conditions. Accurate monitoring of its functioning often enables early detection of various diseases related to disorders in skin microcirculation. To expand the scope of capillaroscopy application, it is reasonable to visualize and assess blood microcirculation exactly in the areas of inflamed skin. Body vibrations, breathing, non-flat skin surface and other factors hamper the application of conventional capillaroscopes outside the nailfold area. In this paper, we propose an exoscope-based optical system for high-quality non-invasive computational imaging of capillary network in various areas of the body. Accurate image matching and tracking temporal intensity variations allow detecting the presence of blood pulsations, precise mapping of capillaries and photoplethysmogram acquisition. We have demonstrated the efficiency of the proposed approach experimentally by in vivo mapping and analysis of microvessels in wrist, forearm, upper-arm, breast and hip areas. We believe that the developed system will increase the diagnostic value of video capillaroscopy in clinical practice.

Blood Vessel Imaging at Pre-Larval Stages of Zebrafish Embryonic Development.

The zebrafish (Danio rerio) is an increasingly popular animal model biological system. In cardiovascular research, it has been used to model specific cardiac phenomena as well as to identify novel therapies for human cardiovascular disease. While the zebrafish cardiovascular system functioning is well examined at larval stages, the mechanisms by which vessel activity is initiated remain a subject of intense investigation. In this research, we report on an in vivo stain-free blood vessel imaging technique at pre-larval stages of zebrafish embryonic development. We have developed the algorithm for the enhancement, alignment and spatiotemporal analysis of bright-field microscopy images of zebrafish embryos. It enables the detection, mapping and quantitative characterization of cardiac activity across the whole specimen. To validate the proposed approach, we have analyzed multiple data cubes, calculated vessel images and evaluated blood flow velocity and heart rate dynamics in the absence of any anesthesia. This non-invasive technique may shed light on the mechanism of vessel activity initiation and stabilization as well as the cardiovascular system's susceptibility to environmental stressors at early developmental stages.

Video capillaroscopy clarifies mechanism of the photoplethysmographic waveform appearance.

Photoplethysmography (PPG) devices are widely used in clinical practice but the origin of PPG signal is still under debating. The classical theory assumes that the PPG waveform stems from variations of blood volume in pulsating arteries. In this research we analysed high-speed video recordings of capillaries in a fingernail bed. It was found that speed of erythrocytes in capillaries has pronounced modulation in time, which follows variations of instantaneous blood pressure in arteries. However, the mean speed significantly differs even for neighbour capillaries whereas change of the speed occurs in phase for the most of capillaries. Moreover, the light intensity remitted from the papillary dermis is also modulated at the heartbeat frequency displaying significant correlation with waveforms of the RBC speed. Obtained results can hardly be explained by the classical theory of PPG signal formation. Shallow penetrating visible light acquires modulation of erythrocytes density in the capillary bed without interacting with deeper situated pulsating arteries. Therefore, the capillary bed could serve as a distributed sensor for monitor the status of deep vessels. Better understanding of the photoplethysmography basis will result in a wider range of applications of this fast growing technology in both medical and research practice.

Grid-based Continual Analysis of Molecular Interior for Drug Discovery, QSAR and QSPR.

BACKGROUND: In 1979, R.D.Cramer and M.Milne made a first realization of 3D comparison of molecules by aligning them in space and by mapping their molecular fields to a 3D grid. Further, this approach was developed as the DYLOMMS (Dynamic Lattice- Oriented Molecular Modelling System) approach. In 1984, H.Wold and S.Wold proposed the use of partial least squares (PLS) analysis, instead of principal component analysis, to correlate the field values with biological activities. Then, in 1988, the method which was called CoMFA (Comparative Molecular Field Analysis) was introduced and the appropriate software became commercially available. Since 1988, a lot of 3D QSAR methods, algorithms and their modifications are introduced for solving of virtual drug discovery problems (e.g., CoMSIA, CoMMA, HINT, HASL, GOLPE, GRID, PARM, Raptor, BiS, CiS, ConGO,). All the methods can be divided into two groups (classes):1. Methods studying the exterior of molecules; 2) Methods studying the interior of molecules. METHODS: A series of grid-based computational technologies for Continual Molecular Interior analysis (CoMIn) are invented in the current paper. The grid-based analysis is fulfilled by means of a lattice construction analogously to many other grid-based methods. The further continual elucidation of molecular structure is performed in various ways. (i) In terms of intermolecular interactions potentials. This can be represented as a superposition of Coulomb, Van der Waals interactions and hydrogen bonds. All the potentials are well known continual functions and their values can be determined in all lattice points for a molecule. (ii) In the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the first principles, an original quantum free-orbital approach AlteQ is proposed. All the functions can be calculated using a quantum approach at a sufficient level of theory and their values can be determined in all lattice points for a molecule. Then, the molecules of a dataset can be superimposed in the lattice for the maximal coincidence (or minimal deviations) of the potentials (i) or the quantum functions (ii). RESULTS: The methods and criteria of the superimposition are discussed. After that a functional relationship between biological activity or property and characteristics of potentials (i) or functions (ii) is created. The methods of the quantitative relationship construction are discussed. New approaches for rational virtual drug design based on the intermolecular potentials and quantum functions are invented. All the invented methods are realized at www.chemosophia.com web page. CONCLUSION: Therefore, a set of 3D QSAR approaches for continual molecular interior study giving a lot of opportunities for virtual drug discovery, virtual screening and ligand-based drug design are invented. The continual elucidation of molecular structure is performed in the terms of intermolecular interactions potentials and in the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the first principles, an original quantum free-orbital approach AlteQ is proposed. The methods of the quantitative relationship construction are discussed. New approaches for rational virtual drug design based on the intermolecular potentials and quantum functions are invented. All the invented methods are realized at www.chemosophia.com web page.