Insights into polycrystalline microstructure of blood films with 3D Mueller matrix imaging approach.

This study introduces a novel approach in the realm of liquid biopsies, employing a 3D Mueller-matrix (MM) image reconstruction technique to analyze dehydrated blood smear polycrystalline structures. Our research centers on exploiting the unique optical anisotropy properties of blood proteins, which undergo structural alterations at the quaternary and tertiary levels in the early stages of diseases such as cancer. These alterations manifest as distinct patterns in the polycrystalline microstructure of dried blood droplets, offering a minimally invasive yet highly effective method for early disease detection. We utilized a groundbreaking 3D MM mapping technique, integrated with digital holographic reconstruction, to perform a detailed layer-by-layer analysis of partially depolarizing dry blood smears. This method allows us to extract critical optical anisotropy parameters, enabling the differentiation of blood films from healthy individuals and prostate cancer patients. Our technique uniquely combines polarization-holographic and differential MM methodologies to spatially characterize the 3D polycrystalline structures within blood films. A key advancement in our study is the quantitative evaluation of optical anisotropy maps using statistical moments (first to fourth orders) of linear and circular birefringence and dichroism distributions. This analysis provides a comprehensive characterization of the mean, variance, skewness, and kurtosis of these distributions, crucial for identifying significant differences between healthy and cancerous samples. Our findings demonstrate an exceptional accuracy rate of over 90 % for the early diagnosis and staging of cancer, surpassing existing screening methods. This high level of precision and the non-invasive nature of our technique mark a significant advancement in the field of liquid biopsies. It holds immense potential for revolutionizing cancer diagnosis, early detection, patient stratification, and monitoring, thereby greatly enhancing patient care and treatment outcomes. In conclusion, our study contributes a pioneering technique to the liquid biopsy domain, aligning with the ongoing quest for non-invasive, reliable, and efficient diagnostic methods. It opens new avenues for cancer diagnosis and monitoring, representing a substantial leap forward in personalized medicine and oncology.

Beyond life: Exploring hemodynamic patterns in postmortem mice brains.

We utilize Laser Speckle Contrast Imaging (LSCI) for visualizing cerebral blood flow in mice during and post-cardiac arrest. Analyzing LSCI images, we noted temporal blood flow variations across the brain surface for hours postmortem. Fast Fourier Transform (FFT) analysis depicted blood flow and microcirculation decay post-death. Continuous Wavelet Transform (CWT) identified potential cerebral hemodynamic synchronization patterns. Additionally, non-negative matrix factorization (NMF) with four components segmented LSCI images, revealing structural subcomponent alterations over time. This integrated approach of LSCI, FFT, CWT, and NMF offers a comprehensive tool for studying cerebral blood flow dynamics, metaphorically capturing the 'end of the tunnel' experience. Results showed primary postmortem hemodynamic activity in the olfactory bulbs, followed by blood microflow relocations between somatosensory and visual cortical regions via the superior sagittal sinus. This method opens new avenues for exploring these phenomena, potentially linking neuroscientific insights with mysteries surrounding consciousness and perception at life's end.

Incremental residual polarization caused by aging in human skin.

Significance: The study of the effect of aging on the optical properties of biological tissues, in particular polarization, is important in the development of new diagnostic approaches. Aim: This work aims to provide a comprehensive analysis of the factors and mechanisms that contribute to the alteration of skin polarization properties caused by aging, using polarization-sensitive hyperspectral imaging measurements and Monte Carlo simulation. Approach: Our investigation involved both experimental studies of in vivo human skin of volunteers of different ages and computational modeling that accounted for changes in the absorption and scattering properties of the skin model. Specifically, we analyzed alterations in the degree of linear polarization (DOLP) to better understand the impact of aging on skin polarization properties. Results: A statistically significant increase in the DOLP was found for the elderly group. At the same time, there was no correlation between changes in polarization and the calculated blood volume fraction parameter for different ages. According to the simulation results, it was also found that a change in the scattering properties of biological tissues has a more significant effect on the change in polarizing light compared to the change in absorption. Conclusions: The results of the work prove that the sensitivity of polarization imaging to age- or pathological-related skin changes may be primarily due to changes in scattering, which in turn is associated with changes in the collagen fibers of the dermis. The proposed technique shows promise for in vivo non-invasive real-time assessment of age-associated skin changes and can also be extended to monitor changes associated with the development of age-related pathologies.

Exploring the evolution of circular polarized light backscattered from turbid tissue-like disperse medium utilizing generalized Monte Carlo modeling approach with a combined use of Jones and Stokes-Mueller formalisms.

Significance: Phase retardation of circularly polarized light (CPL), backscattered by biological tissue, is used extensively for quantitative evaluation of cervical intraepithelial neoplasia, presence of senile Alzheimer's plaques, and characterization of biotissues with optical anisotropy. The Stokes polarimetry and Mueller matrix approaches demonstrate high potential in definitive non-invasive cancer diagnosis and tissue characterization. The ultimate understanding of CPL interaction with tissues is essential for advancing medical diagnostics, optical imaging, therapeutic applications, and the development of optical instruments and devices. Aim: We investigate propagation of CPL within turbid tissue-like scattering medium utilizing a combination of Jones and Stokes-Mueller formalisms in a Monte Carlo (MC) modeling approach. We explore the fundamentals of CPL memory effect and depolarization formation. Approach: The generalized MC computational approach developed for polarization tracking within turbid tissue-like scattering medium is based on the iterative solution of the Bethe-Salpeter equation. The approach handles helicity response of CPL scattered in turbid medium and provides explicit expressions for assessment of its polarization state. Results: Evolution of CPL backscattered by tissue-like medium at different conditions of observation in terms of source-detector configuration is assessed quantitatively. The depolarization of light is presented in terms of the coherence matrix and Stokes-Mueller formalism. The obtained results reveal the origins of the helicity flip of CPL depending on the source-detector configuration and the properties of the medium and are in a good agreement with the experiment. Conclusions: By integrating Jones and Stokes-Mueller formalisms, the combined MC approach allows for a more complete representation of polarization effects in complex optical systems. The developed model is suitable to imitate propagation of the light beams of different shape and profile, including Gaussian, Bessel, Hermite-Gaussian, and Laguerre-Gaussian beams, within tissue-like medium. Diverse configuration of the experimental conditions, coherent properties of light, and peculiarities of polarization can be also taken into account.

Mueller-matrix imaging polarimetry elevated by wavelet decomposition and polarization-singular processing for analysis of specific cancerous tissue pathology.

Significance: Mueller-matrix polarimetry is a powerful method allowing for the visualization of malformations in biological tissues and quantitative evaluation of alterations associated with the progression of various diseases. This approach, in fact, is limited in observation of spatial localization and scale-selective changes in the poly-crystalline compound of tissue samples. Aim: We aimed to improve the Mueller-matrix polarimetry approach by implementing the wavelet decomposition accompanied with the polarization-singular processing for express differential diagnosis of local changes in the poly-crystalline structure of tissue samples with various pathology. Approach: Mueller-matrix maps obtained experimentally in transmitted mode are processed utilizing a combination of a topological singular polarization approach and scale-selective wavelet analysis for quantitative assessment of the adenoma and carcinoma histological sections of the prostate tissues. Results: A relationship between the characteristic values of the Mueller-matrix elements and singular states of linear and circular polarization is established within the framework of the phase anisotropy phenomenological model in terms of linear birefringence. A robust method for expedited (up to ∼15 min) polarimetric-based differential diagnosis of local variations in the poly-crystalline structure of tissue samples containing various pathology abnormalities is introduced. Conclusions: The benign and malignant states of the prostate tissue are identified and assessed quantitatively with a superior accuracy provided by the developed Mueller-matrix polarimetry approach.

Impact of Plasmonic Nanoparticles on Poikilocytosis and Microrheological Properties of Erythrocytes.

Plasmonic nanoparticles (NP) possess great potential in photothermal therapy and diagnostics. However, novel NP require a detailed examination for potential toxicity and peculiarities of interaction with cells. Red blood cells (RBC) are important for NP distribution and the development of hybrid RBC-NP delivery systems. This research explored RBC alterations induced by noble (Au and Ag) and nitride-based (TiN and ZrN) laser-synthesized plasmonic NP. Optical tweezers and conventional microscopy modalities indicated the effects arising at non-hemolytic levels, such as RBC poikilocytosis, and alterations in RBC microrheological parameters, elasticity and intercellular interactions. Aggregation and deformability significantly decreased for echinocytes independently of NP type, while for intact RBC, all NP except Ag NP increased the interaction forces but had no effect on RBC deformability. RBC poikilocytosis promoted by NP at concentration 50 µg mL-1 was more pronounced for Au and Ag NP, compared to TiN and ZrN NP. Nitride-based NP demonstrated better biocompatibility towards RBC and higher photothermal efficiency than their noble metal counterparts.

Terahertz-to-infrared converters for imaging the human skin cancer: challenges and feasibility.

Purpose: Terahertz (THz) medical imaging is a promising noninvasive technique for monitoring the skin's conditions, early detection of the human skin cancer, and recovery from burns and wounds. It can be applied for visualization of the healing process directly through clinical dressings and restorative ointments, minimizing the frequency of dressing changes. The THz imaging technique is cost effective, as compared to the magnetic resonance method. Our aim was to develop an approach capable of providing better image resolution than the commercially available THz imaging cameras. Approach: The terahertz-to-infrared (THz-to-IR) converters can visualize the human skin cancer by converting the latter's specific contrast patterns recognizable in THz radiation range into IR patterns, detectable by a standard IR imaging camera. At the core of suggested THz-to-IR converters are flat matrices transparent both in the THz range to be visualized and in the operating range of the IR camera, these matrices contain embedded metal nanoparticles (NPs), which, when irradiated with THz rays, convert the energy of THz photons into heat and become nanosources of IR radiation detectable by an IR camera. Results: The ways of creating the simplest converter, as well as a more complex converter with wider capabilities, are considered. The first converter is a gelatin matrix with gold 8.5-nm diameter NPs, and the second is a polystyrene matrix with 2-nm diameter NPs from copper-nickel MONEL® alloy 404. Conclusions: An approach with a THz-to-IR converter equipped with an IR camera is promising in that it could provide a better image of oncological pathology than the commercially available THz imaging cameras do.

Synthesis of Disubstituted Carboxonium Derivatives of Closo-Decaborate Anion [2,6-B10H8O2CC6H5]-: Theoretical and Experimental Study.

A comprehensive study focused on the preparation of disubstituted carboxonium derivatives of closo-decaborate anion [2,6-B10H8O2CC6H5]- was carried out. The proposed synthesis of the target product was based on the interaction between the anion [B10H11]- and benzoic acid C6H5COOH. It was shown that the formation of this product proceeds stepwise through the formation of a mono-substituted product [B10H9OC(OH)C6H5]-. In addition, an alternative one-step approach for obtaining the target derivative is postulated. The structure of tetrabutylammonium salts of carboxonium derivative ((C4H9)4N)[2,6-B10H8O2CC6H5] was established with the help of X-ray structure analysis. The reaction pathway for the formation of [2,6-B10H8O2CC6H5]- was investigated with the help of density functional theory (DFT) calculations. This process has an electrophile induced nucleophilic substitution (EINS) mechanism, and intermediate anionic species play a key role. Such intermediates have a structure in which one boron atom coordinates two hydrogen atoms. The regioselectivity for the process of formation for the 2,6-isomer was also proved by theoretical calculations. Generally, in the experimental part, the simple and available approach for producing disubstituted carboxonium derivative was introduced, and the mechanism of this process was investigated with the help of theoretical calculations. The proposed approach can be applicable for the preparation of a wide range of disubstituted derivatives of closo-borate anions.

Brillouin Interaction between Two Optical Modes Selectively Excited in Weakly Guiding Multimode Optical Fibers.

A multimode optical fiber supports excitation and propagation of a pure single optical mode, i.e., the field pattern that satisfies the boundary conditions and does not change along the fiber. When two counterpropagating pure optical modes are excited, they could interact through the stimulated Brillouin scattering (SBS) process. Here, we present a simple theoretical formalism describing SBS interaction between two individual optical modes selectively excited in an acoustically isotropic multimode optical fiber. Employing a weakly guiding step-index fiber approach, we have built an analytical expression for the spatial distribution of the sound field amplitude in the fiber core and explored the features of SBS gain spectra, describing the interaction between modes of different orders. In this way, we give a clear insight into the sound propagation effects accompanying SBS in multimode optical fibers, and demonstrate their specific contributions to the SBS gain spectrum.

Diagnosis of Skin Vascular Complications Revealed by Time-Frequency Analysis and Laser Doppler Spectrum Decomposition.

Nowadays, photonics-based techniques are used extensively in various applications, including functional clinical diagnosis, progress monitoring in treatment, and provision of metrological control. In fact, in the frame of practical implementation of optical methods, such as laser Doppler flowmetry (LDF), the qualitative interpretation and quantitative assessment of the detected signal remains vital and urgently required. In the conventional LDF approach, the key measured parameters, index of microcirculation and perfusion rate, are proportional to an averaged concentration of red blood cells (RBC) and their average velocity within a diagnostic volume. These quantities compose mixed signals from different vascular beds with a range of blood flow velocities and are typically expressed in relative units. In the current paper we introduce a new signal processing approach for the decomposition of LDF power spectra in terms of ranging blood flow distribution by frequency series. The developed approach was validated in standard occlusion tests conducted on healthy volunteers, and applied to investigate the influence of local pressure rendered by a probe on the surface of the skin. Finally, in limited clinical trials, we demonstrate that the approach can significantly improve the diagnostic accuracy of detection of microvascular changes in the skin of the feet in patients with Diabetes Mellitus type 2, as well as age-specific changes. The results obtained show that the developed approach of LDF signal decomposition provides essential new information about blood flow and blood microcirculation and has great potential in the diagnosis of vascular complications associated with various diseases.

Non-Covalent Interactions in the Crystal Structures of Perbrominated Sulfonium Derivatives of the closo-Decaborate Anion.

A new series of compounds based on perbrominated disubstituted sulfonium derivatives of the closo-decaborate anion (n-Bu4N)[2-B10Br9SR2] (R = n-Pr, i-Pr, n-Bu, n-C8H17, n-C12H25, n-C18H37) was obtained, characterised by modern physicochemical methods of analysis. According to the results of an X-ray diffraction study, some of the anions and solvate molecules were disordered. The cations (n-Bu4N)+ and anions [2-B10Br9SR2]- were associated via C-H…Br and H…H contacts. In addition, Br…Br interactions between anions were revealed. The role of these contacts was analysed in terms of Hirshfeld surface analysis, QTAIM theory and the NCI method using quantum chemical calculations. An increase in the size of the alkyl R moiety led to significant strengthening of the total energy of H…H interactions. In the case of R = -n-C18H37, a parallel mutual orientation of alkyl moieties was established that was similar to the packing of salts of fatty acids. The nature of C-H…Br and Br…Br interionic interactions was found to be attractive, in contrast to the repulsive nature of intermolecular Br…Br interactions.

Optogenetic Control of Bacterial Expression by Red Light.

In optogenetics, as in nature, sensory photoreceptors serve to control cellular processes by light. Bacteriophytochrome (BphP) photoreceptors sense red and far-red light via a biliverdin chromophore and, in response, cycle between the spectroscopically, structurally, and functionally distinct Pr and Pfr states. BphPs commonly belong to two-component systems that control the phosphorylation of cognate response regulators and downstream gene expression through histidine kinase modules. We recently demonstrated that the paradigm BphP from Deinococcus radiodurans exclusively acts as a phosphatase but that its photosensory module can control the histidine kinase activity of homologous receptors. Here, we apply this insight to reprogram two widely used setups for bacterial gene expression from blue-light to red-light control. The resultant pREDusk and pREDawn systems allow gene expression to be regulated down and up, respectively, uniformly under red light by 100-fold or more. Both setups are realized as portable, single plasmids that encode all necessary components including the biliverdin-producing machinery. The triggering by red light affords high spatial resolution down to the single-cell level. As pREDusk and pREDawn respond sensitively to red light, they support multiplexing with optogenetic systems sensitive to other light colors. Owing to the superior tissue penetration of red light, the pREDawn system can be triggered at therapeutically safe light intensities through material layers, replicating the optical properties of the skin and skull. Given these advantages, pREDusk and pREDawn enable red-light-regulated expression for diverse use cases in bacteria.

Multiplexed spatially-focused localization of light in adipose biological tissues.

Last decades the effects of localization and focusing of light in turbid randomly inhomogeneous tissue-like scattering medium have been attracting a particular attention. Weak localization of light in disordered and weakly ordered biological tissue, polarization memory effect, correlations in transmission matrices, focusing light by wavefronts shaping have been widely exploited. Here, we represent an experimentally observed and theoretically confirmed new type of spatial localization of light within biological tissues. General description of the observed phenomenon based on Monte Carlo ray tracing model is provided. We find that innate body arrangements of individual adipocytes can act as a cascade of quasi-ordered microscale lenses confining propagation of light within adipose tissues similar to lens lightguides. The observed spatially-resolved longitudinal multi-focusing of light within disordered adipose biological tissues can naturally lead greater spatial control and enhance light-tissue interactions.

Luminescent upconversion nanoparticles evaluating temperature-induced stress experienced by aquatic organisms owing to environmental variations.

Growing anthropogenic activities are significantly influencing the environment and especially aquatic ecosystems. Therefore, there is an increasing demand to develop techniques for monitoring and assessing freshwater habitat changes so that interventions can prevent irrevocable damage. We explore an approach for screening the temperature-induced stress experienced by aquatic organisms owing to environmental variations. Luminescent spectra of upconversion [Y2O3: Yb, Er] particles embedded within Caridina multidentata shrimps are measured, while ambient temperature gradient is inducing stress conditions. The inverse linear dependence of the logarithmic ratio of the luminescence intensity provides an effective means for temperature evaluation inside aquatic species in vivo. The measured luminescence shows high photostability on the background of the complete absence of biotissues' autofluorescence, as well as no obscuration of the luminescence signal from upconversion particles. Current approach of hybrid sensing has a great potential for monitoring variations in aquatic ecosystems driven by climate changes and pollution.

Protonation of Borylated Carboxonium Derivative [2,6-B10H8O2CCH3]-: Theoretical and Experimental Investigation.

The process of protonation of [2,6-B10H8O2CCH3]- was investigated both theoretically and experimentally. The most suitable conditions for protonation of the derivative [2,6-B10H8O2CCH3]- were found. The process of protonation was carried out in the presence of an excess of trifluoromethanesulfonic acid CF3SO3H at room temperature in dichloromethane solution. The structure of the resulting complex [2,6-B10H8O2CCH3*Hfac]0 was established using NMR data and the results of DFT calculations. An additional proton atom Hfac was found to be localized on one of the facets that was opposite the boron atom in a substituted position, and which bonded mainly with one apical boron atom. The main descriptors of the B-Hfac bond were established theoretically using QTAIM and NBO approaches. In addition, the mechanism of [2,6-B10H8O2CCH3]- protonation was investigated.

Photoacoustic Imaging in Biomedicine and Life Sciences.

Photo-acoustic imaging, also known as opto-acoustic imaging, has become a widely popular modality for biomedical applications. This hybrid technique possesses the advantages of high optical contrast and high ultrasonic resolution. Due to the distinct optical absorption properties of tissue compartments and main chromophores, photo-acoustics is able to non-invasively observe structural and functional variations within biological tissues including oxygenation and deoxygenation, blood vessels and spatial melanin distribution. The detection of acoustic waves produced by a pulsed laser source yields a high scaling range, from organ level photo-acoustic tomography to sub-cellular or even molecular imaging. This review discusses significant novel technical solutions utilising photo-acoustics and their applications in the fields of biomedicine and life sciences.

Hemorheological alterations of red blood cells induced by 450-nm and 520-nm laser radiation.

Proper rheological properties of red blood cells (RBC) including flexibility and aggregability are essential for healthy blood microcirculation. Excessive RBC aggregation has been observed to be associated with many pathological conditions and is crucial in acute circulatory problems. Low-level laser radiation (LLLR) has been found to have positive effects on the rheology of human blood, however, the detailed mechanisms of blood photobiomodulation remains unclear. In this study, utilizing the single-cell technique optical tweezers (OT) and traditional light microscopy, the influence of photobiomodulation of human RBC was examined under different conditions of laser irradiation. The results revealed that high radiant exposure (over 170.5 J/cm2 radiant fluence) caused enhanced RBC aggregation and cell shape transformation while the aggregation force between single RBC remained unchanged. LLLR with radiant fluence below 9.5 J/cm2 by 450 nm wavelength improved the RBC deformability, weakened the strength of cell-cell interaction in the RBC disaggregation process, and showed rejuvenating effects on RBC suspended in a harsh cell environment.

Nucleophilic Substitution Reactions in the [B3H8]- Anion in the Presence of Lewis Acids.

As a result of our study on the interaction between the octahydrotriborate anion with nucleophiles (Nu = THF, Ph3P, Ph2P-(CH2)2-PPh2 (dppe), Ph3As, Et3N, PhNH2, C5H5N, CH3CN, Ph2CHCN)) in the presence of a wide range of Lewis acids (Ti(IV), Hf(IV), Zr(IV), Al, Cu(I), Zn, Mn(II), Co(II) halides and iodine), a number of substituted derivatives of the octahydrotriborate anion [B3H7Nu] are obtained. It is found that the use of TiCl4, AlCl3, ZrCl4, HfCl4, CuCl and iodine leads to the highest product yields. In this case, it is most likely that the reaction proceeds through the formation of an intermediate [B3H7-HMXnx], which was detected by NMR spectroscopy. The structures of [Ph3P·B3H7] and [PhNH2·B3H7] were determined by X-ray diffraction.

Screening of Alzheimer's Disease With Multiwavelength Stokes Polarimetry in a Mouse Model.

The minimum histological criterion for the diagnostics of Alzheimer's disease (AD) in tissue is the presence of senile plaques and neurofibrillary tangles in specific brain locations. The routine procedure of morphological analysis implies time-consuming and laborious steps including sectioning and staining of formalin-fixed paraffin-embedded (FFPE) tissue. We developed a multispectral Stokes polarimetric imaging approach that allows characterization of FFPE brain tissue samples to discern the stages of AD progression without sectioning and staining the tissue. The Stokes polarimetry approach is highly sensitive to structural alterations of brain tissue, particularly to the changes in light scattering and birefringence. We present the results of the label-free non-destructive screening of FFPE mouse brain tissue and show several polarization metrics that demonstrate statistically significant differences for tissues at different stages of AD.

Optical anisotropy composition of benign and malignant prostate tissues revealed by Mueller-matrix imaging.

A Mueller matrix imaging approach is employed to disclose the three-dimensional composition framework of optical anisotropy within cancerous biotissues. Visualized by the Mueller matrix technique spatial architecture of optical anisotropy of tissues is characterised by high-order statistical moments. Thus, quantitative analysis of the spatial distribution of optical anisotropy, such as linear and circular birefringence and dichroism, is revealed by using high-order statistical moments, enabling definitively discriminate prostate adenoma and carcinoma. The developed approach provides greater (>90%) accuracy of diagnostic achieved by using either the 3-rd or 4-th order statistical moments of the linear anisotropy parameters. Noticeable difference is observed between prostate adenoma and carcinoma tissue samples in terms of the extinction coefficient and the degree of depolarisation. Juxtaposition to other optical diagnostic modalities demonstrates the greater accuracy of the approach described herein, paving the way for its wider application in cancer diagnosis and tissue characterization.