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Nowadays, many biodegradable materials are offered for biomedical applications, but there are only a few in vivo methods for their detection and monitoring. In this work, implants based on biodegradable polyester copolymers were labeled with indocyanine green (ICG) for fluorescence imaging in combination with tissue optical clearing (TOC) and magnetic resonance imaging (MRI). The results include in vitro degradation modeling followed by in vivo imaging of copolymer samples that were subcutaneously implanted in BALB/c mice. TOC with 70% glycerol has been demonstrated to significantly improve sample visualization. The TOC efficiency parameter Q demonstrated the variability of effects correlating with the timing of follow-up in the postimplantation period. It has been shown that nonhealing wounds, peri-implantation inflammation, or fibrosis, confirmed by MRI, affect the effectiveness of TOC in the range from Q = -30% to 70%., (© 2025 Wiley‐VCH GmbH.)

The paper presents the results of modern research on the effects of electromagnetic terahertz radiation in the frequency range 0.5-100 THz at different levels of power density and exposure time on the viability of normal and cancer cells. As an accompanying tool for monitoring the effect of radiation on biological cells and tissues, spectroscopic research methods in the terahertz frequency range are described, and attention is focused on the possibility of using the spectra of interstitial water as a marker of pathological processes. The problem of the safety of terahertz radiation for the human body from the point of view of its effect on the structures and systems of biological cells is also considered., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Diabetes mellitus (DM), a chronic metabolic disorder that adversely affects the blood-brain barrier (BBB) and microglial function in the central nervous system (CNS), contributing to neuronal damage and neurodegenerative diseases. However, the underlying molecular mechanisms linking diabetes to BBB dysfunction and microglial dysregulation remain poorly understood. Here, we assessed the impacts of diabetes on BBB and microglial reactivity and investigated its mechanisms. We found diabetes severely disrupted the BBB integrity and microglial response to vascular injury. We also revealed a potential relationship between BBB disruption and impaired microglial function, whereby increasing BBB permeability led to a downregulation of microglial P2RY12 expression, thereby impairing microglial protection against cerebrovascular injury. Understanding these mechanisms may contribute to the developing of therapeutic strategies for diabetes-related neurological complications., (© 2025 Wiley‐VCH GmbH.)

Objectives: The paper focuses on the development of technology of adipose tissue optical clearing using different complex hyperosmotic optical clearing agents and tissue permeability enhancers., Methods: To quantify optical clearing efficiency, reduced scattering coefficient was estimated from the ex vivo spatially resolved backreflectance measurements using a multi-distant fiber optical device. Tissue morphology modification was monitored with the help of histological studies., Results: Kinetics and efficiency of the optical clearing were evaluated for ex vivo abdominal fat tissue at action of dimethyl sulfoxide, diatrizoic acid, metrizoic acid, sucrose, and fructose solutions accompanied by tissue permeability enhancers, such as various modes of fractional laser microablation and sonophoresis and their combinations. Histological studies allowed us to find agents that cause minimal morphological changes of the adipose tissue., Conclusions: Maximal optical clearing efficiency of 83.5% was observed for the samples subjected to action of the fructose-ethanol solution during 90 min in combination with gentle modes of fractional laser microablation and sonophoresis., (© 2024 Wiley Periodicals LLC.)

Advanced optical imaging provides a powerful tool for the structural and functional analysis of tissues with high resolution and contrast, but the imaging performance decreases as light propagates deeper into the tissue. Tissue optical clearing technique demonstrates an innovative way to realize deep-tissue imaging and have emerged substantially in the last two decades. Here, we briefly reviewed the basic principles of tissue optical clearing techniques in the view of delivery strategies via either free diffusion or external forces-driven advection, and the commonly-used optical techniques for monitoring kinetics of clearing agents in tissue, as well as their ex vivo to in vivo applications in multiple biomedical research fields. With future efforts on the even distribution of both clearing agents and probes, excavation of more effective clearing agents, and automation of tissue clearing processes, tissue optical clearing should provide more insights into the fundamental questions in biological events clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination., (© 2024 Wiley‐VCH GmbH.)

A Mueller matrix covers all the polarization information of the measured sample, however the combination of its 16 elements is sometimes not intuitive enough to describe and identify the key characteristics of polarization changes. Within the Poincaré sphere system, this study achieves a spatial representation of the Mueller matrix: the Global-Polarization Stokes Ellipsoid (GPSE). With the help of Monte Carlo simulations combined with anisotropic tissue models, three basic characteristic parameters of GPSE are proposed and explained, where the V parameter represents polarization maintenance ability, and the E and D † parameters represent the degree of anisotropy. Furthermore, based on GPSE system, a dynamic analysis of skeletal muscle dehydration process demonstrates the monitoring effect of GPSE from an application perspective, while confirming its robustness and accuracy., (© 2024. The Author(s).)

The study encompasses an investigation of optical, photothermal and biocompatibility properties of a composite consisting of golden cores surrounded by superparamagnetic CoFe 2 O 4 nanoparticles. Accompanied with the experiment, the computational modeling reveals that each adjusted magnetic nanoparticle redshifts the plasmon resonance frequency in gold and nonlinearly increases the extinction cross-section at ~800 nm. The concentration dependent photothermal study demonstrates a temperature increase of 8.2 K and the photothermal conversion efficiency of 51% for the 100 μg/mL aqueous solution of the composite nanoparticles, when subjected to a laser power of 0.5 W at 815 nm. During an in vitro photothermal therapy, a portion of the composite nanoparticles, initially seeded at this concentration, remained associated with the cells after washing. These retained nanoparticles effectively heated the cell culture medium, resulting in a 22% reduction in cell viability after 15 min of the treatment. The composite features a potential in multimodal magneto-plasmonic therapies., (© 2024 Wiley‐VCH GmbH.)

Inflammatory dermatoses represent a global problem with increasing prevalence and recurrence among the world population. Topical glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs in dermatology due to a wide range of their therapeutic actions, which, however, have numerous local and systemic side effects. Hence, there is a growing need to create new delivery systems for GCs, ensuring the drug localization in the pathological site, thus increasing the effectiveness of therapy and lowering the risk of side effects. Here, we propose a novel topical particulate formulation for the GC clobetasol propionate (CP), based on the use of porous calcium carbonate (CaCO 3 ) carriers in the vaterite crystalline form. The designed carriers contain a substantially higher CP amount than conventional dosage forms used in clinics (4.5% w/w vs. 0.05% w/w) and displayed a good biocompatibility and effective cellular uptake when studied in fibroblasts in vitro . Hair follicles represent an important reservoir for the GC accumulation in skin and house the targets for its action. In this study, we demonstrated successful delivery of the CP-loaded carriers (CP-CaCO 3 ) into the hair follicles of rats in vivo using optical coherent tomography (OCT). Importantly, the OCT monitoring revealed the gradual intrafollicular degradation of the carriers within 168 h with the most abundant follicle filling occurring within the first 48 h. Biodegradability makes the proposed system especially promising when searching for new CP formulations with improved safety and release profile. Our findings evidenced the great potential of the CaCO 3 carriers in improving the dermal bioavailability of this poorly water-soluble GC.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis., (© 2024. The Author(s).)

We studied grafted tumors obtained by subcutaneous implantation of kidney cancer cells into male white rats. Gold nanorods with a plasmon resonance of about 800 nm were injected intratumorally for photothermal heating. Experimental irradiation of tumors was carried out percutaneously using a near-infrared diode laser. Changes in the optical properties of the studied tissues in the spectral range 350-2200 nm under plasmonic photothermal therapy (PPT) were studied. Analysis of the observed changes in the absorption bands of water and hemoglobin made it possible to estimate the depth of thermal damage to the tumor. A significant decrease in absorption peaks was observed in the spectrum of the upper peripheral part and especially the tumor capsule. The obtained changes in the optical properties of tissues under laser irradiation can be used to optimize laboratory and clinical PPT procedures., (© 2024 Wiley‐VCH GmbH.)

Optical clearing agents (OCAs) are substances that temporarily modify tissue's optical properties, enabling better imaging and light penetration. This study aimed to assess the impact of OCAs on the nail bed and blood using in vivo and in vitro optical methods. In the in vivo part, OCAs were applied to the nail bed, and optical coherence tomography and optical digital capillaroscopy were used to evaluate their effects on optical clearing and capillary blood flow, respectively. In the in vitro part, the collected blood samples were incubated with the OCA and blood aggregation properties were estimated using diffuse light scattering techniques. The results indicate that OCAs significantly influence the optical properties of the nail bed and blood microrheology. These findings suggest that OCAs hold promise for improving optical imaging and diagnostics, particularly for nail bed applications, and can modify blood microrheology., (© 2024 Wiley-VCH GmbH.)

The broadband absorption coefficient spectrum of the rabbit lung presents some particular characteristics that allow the identification of the chromophores in this tissue. By performing a weighted combination of the absorption spectra of water, hemoglobin, DNA, proteins and the pigments melanin and lipofuscin, it was possible to obtain a good match to the experimental absorption spectrum of the lung. Such reconstruction provided reasonable information about the contents of the tissue components in the lung tissue, and allowed to identify a similar accumulation of melanin and lipofuscin., (© 2024 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

With the objective of developing new methods to acquire diagnostic information, the reconstruction of the broadband absorption coefficient spectra (μ a [λ]) of healthy and chromophobe renal cell carcinoma kidney tissues was performed. By performing a weighted sum of the absorption spectra of proteins, DNA, oxygenated, and deoxygenated hemoglobin, lipids, water, melanin, and lipofuscin, it was possible to obtain a good match of the experimental μ a (λ) of both kidney conditions. The weights used in those reconstructions were estimated using the least squares method, and assuming a total water content of 77% in both kidney tissues, it was possible to calculate the concentrations of the other tissue components. It has been shown that with the development of cancer, the concentrations of proteins, DNA, oxygenated hemoglobin, lipids, and lipofuscin increase, and the concentration of melanin decreases. Future studies based on minimally invasive spectral measurements will allow cancer diagnosis using the proposed approach., (© 2024 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

The results of in vivo immersion optical clearing of human skin under the action of two different optical clearing agents (OCAs), such as an aqueous sucrose solution and a radiographic contrast agent Omnipaque™ 300 (iohexol), were obtained with the use of optical coherence tomography (OCT) method. The rate of reduction of light scattering coefficient, obtained through an averaged A-scan of the OCT image in the region of dermis within the depths from 350 to 700 μm, were determined to evaluate the efficiency of optical clearing (EOC). The correlations between the EOC and the energy of intermolecular interaction of OCAs with a fragment of collagen peptide have been established as a result of molecular modeling by quantum chemistry methods HF/STO3G/DFT/B3LYP/6-311G(d) of a number of OCAs (glycerol, iohexol, sucrose, ribose, fructose, glucose) with mimetic peptide of collagen (GPH) 3 ., (© 2023 Wiley-VCH GmbH.)

In this paper, we study a pattern formation in the epidermal layer of skin during tumor development and appearance of a binary surface consisting of healthy and cancer cells forming Turing patterns under external osmotic pressure. The basic methodology of introducing the external influences, for example, time-targeted drug therapy or radiation exposure, influence of electromagnetic fields, laser radiation or other tumor-targeting physical influences act differently in different phases of the cell cycle. In some cases, this can lead to a slowdown in the growth of cancer cells, and sometimes vice versa. Therefore, it is of particular interest to choose the right parameters such as starting time of external pressure, its magnitude and duration depending on the cell cycle of developing cancer cells. We propose a biologically inspired model that allows us to simulate the growth of cancer cells under conditions of osmotic pressure. We divide this growth into two phases. The first is characterized by active cell division, and the second by their growth. In this article, we introduce two types of pressure: short-term and long-term, and looked at what this leads to in different phases. We have found an interesting result, that there are some resonant points in time both in the first and second phases, when the introduction of additional pressure leads to the most significant slowdown in the growth of cancer cells., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Photodynamic therapy (PDT) is a well-established cancer treatment method that employs light to generate reactive oxygen species (ROS) causing oxidative damage to cancer cells. Nevertheless, PDT encounters challenges due to its oxygen-dependent nature, which makes it less effective in hypoxic tumor environments. To address this issue, we have developed a novel nanocomposite known as AuNC@BBR@Ghost. This nanocomposite combines the advantageous features of erythrocyte ghost membranes, the photoresponsive properties of gold nanoclusters (AuNC) and the anticancer characteristics of Berberine (BBR) for cancer treatment. Our synthesized AuNC efficiently produce ROS, with a 25% increase in efficiency when exposed to near-infrared (NIR) irradiation. By harnessing the oxygen-carrying capacity of erythrocyte ghost cells, AuNC@BBR@Ghost demonstrates a significant improvement in ROS generation, achieving an 80% efficiency. Furthermore, the AuNC exhibit tunable emission wavelengths due to their excellent fluorescent properties. In normoxic conditions, treatment of A549 lung carcinoma cells with AuNC@BBR@Ghost followed by exposure to 808 nm NIR irradiation results in a notable increase in intracellular ROS levels, accelerating cell death. In hypoxic conditions, when A549 cells were treated with AuNC@BBR@Ghost, the erythrocyte ghost acted as an oxygen supplement due to the residual hemoglobin, alleviating hypoxia and enhancing the nanocomposite's sensitivity to PDT treatment. Thus, the AuNC@BBR@Ghost nanocomposite achieves an improved effect by combining the advantageous properties of its individual components, resulting in enhanced ROS generation and adaptability to hypoxic conditions. This innovative approach successfully overcomes PDT's limitations, making AuNC@BBR@Ghost a promising nanotheranostic agent with significant potential for advanced cancer therapy., Competing Interests: The authors declare there are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Correct classification of skin lesions is a key step in skin cancer screening, which requires high accuracy and interpretability. This paper proposes a multimodal method for differentiating various clinical forms of basal cell carcinoma and benign neoplasms that includes machine learning. This study was conducted on 37 neoplasms, including benign neoplasms and five different clinical forms of basal cell carcinoma. The proposed multimodal screening method combines diffuse reflectance spectroscopy, optical coherence tomography and high-frequency ultrasound. Using diffuse reflectance spectroscopy, the coefficients of melanin pigmentation, erythema, hemoglobin content, and the slope coefficient of diffuse reflectance spectroscopy in the wavelength range 650-800 nm were determined. Statistical texture analysis of optical coherence tomography images was used to calculate first- and second-order statistical parameters. The analysis of ultrasound images assessed the shape of the tumor according to parameters such as area, perimeter, roundness and other characteristics. Based on the calculated parameters, a machine learning algorithm was developed to differentiate the various clinical forms of basal cell carcinoma. The proposed algorithm for classifying various forms of basal cell carcinoma and benign neoplasms provided a sensitivity of 70.6 ± 17.3%, specificity of 95.9 ± 2.5%, precision of 72.6 ± 14.2%, F 1 score of 71.5 ± 15.6% and mean intersection over union of 57.6 ± 20.1%. Moreover, for differentiating basal cell carcinoma and benign neoplasms without taking into account the clinical form, the method achieved a sensitivity of 89.1 ± 8.0%, specificity of 95.1 ± 0.7%, F 1 score of 89.3 ± 3.4% and mean intersection over union of 82.6 ± 10.8%.

The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood-brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer's disease. This review provides a comprehensive overview of tPBM. We summarize emerging trends and new discoveries in tPBM based on over one hundred references published in the past 20 years. We discuss the advantages and disadvantages of tPBM and highlight successful experimental and clinical protocols for treating various brain diseases. A better understanding of tPBM mechanisms, the development of guidelines for clinical practice, and the study of dose-dependent and personal effects hold great promise for progress in treating brain diseases., (© 2024 The Authors.)

The biggest obstacle to optical imaging is light attenuation in biological tissues. Conventional clearing techniques, such as agent-based clearing, improve light penetration depth by reducing scattering, but they are hampered by drawbacks including toxicity, low efficiency, slowness, and superficial performance, which prevent them from resolving the attenuation problem on their own. Therefore, quick, safe, and effective procedures have been developed. One of them involves using standing ultrasonic waves to build light waveguides that function effectively in the tissue depth while minimizing scattering. Temporal optical clearing is another agent-free strategy that we introduced in our previous article. Whereas not deep, this technique minimizes both light absorption and scattering by pulse width variation in ultra-short pulse regime. Consequently, it can be a complementary method for ultrasonic optical clearing. In this work, we enhanced the light penetration depth in chicken breast tissue by 10 times (0.67-6.7 cm), setting a record in literature by integrating three clearing methods: agent-based, ultrasound-based, and temporal. Here, optical coherence tomography, Bear-Lambert, and fluorescence tests have been used to study the light penetration depth and optical clearing efficiency. Presented work is an essential step in development of diagnostic techniques for human body, from cells to organs., (© 2023. The Author(s).)

The rapid and accurate diagnosis of cancer is an important topic in clinical medicine. In the present work, an innovative method based on laser-induced breakdown spectroscopy (LIBS) combined with machine learning was developed to distinguish and classify different tumor cell lines. The LIBS spectra of cells were first acquired. Then the spectral pre-processing was performed as well as detailed optimization to improve the classification accuracy. After that, the convolutional neural network (CNN), support vector machine (SVM), and K-nearest neighbors were further compared for the optimized classification ability of tumor cells. Both the CNN algorithm and SVM algorithm have achieved impressive discrimination performances for tumor cells distinguishing, with an accuracy of 97.72%. The results show that the heterogeneity of elements in tumor cells plays an important role in distinguishing the cells. It also means that the LIBS technique can be used as a fast classification method for classifying tumor cells., (© 2023 Wiley-VCH GmbH.)

Photoacoustic flow cytometry is one of the most effective approaches to detect "alien" objects in the bloodstream, including circulating tumor cells, blood clots, parasites, and emboli. However, the possibility of detecting high-amplitude signals from these objects against the background of blood depends on the parameters of the laser pulse. So, the dependencies of photoacoustic signals amplitude and number on laser pulse energy (5-150 μJ), pulse length (1, 2, 5 ns), and pulse repetition rate (2, 5, 10 kHz) for the melanoma cells were investigated. First, the PA responses of a melanoma cell suspension in vitro were measured to directly assess the efficiency of converting laser light into an acoustic signal. After it, the same dependence with the developed murine model based on constant rate melanoma cell injection into the animal blood flow was tested. Both in vivo and in vitro experiments show that signal generation efficiency increases with laser pulse energy above 15 μJ. Shorter pulses, especially 1 ns, provide more efficient signal generation as well as higher pulse rates. A higher pulse rate also provides more efficient signal generation, but also leads to overheating of the skin. The results show the limits where the photoacoustic flow cytometry system can be effectively used for the detection of circulating tumor cells in undiluted blood both for in vitro experiments and for in vivo murine models., (© 2023 International Society for Advancement of Cytometry.)

(1) Background: The use of electronic cigarettes has become widespread in recent years. The use of e-cigarettes leads to milder pathological conditions compared to traditional cigarette smoking. Nevertheless, e-liquid vaping can cause morphological changes in lung tissue, which affects and impairs gas exchange. This work studied the changes in morphological and optical properties of lung tissue under the action of an e-liquid aerosol. To do this, we implemented the "passive smoking" model and created the specified concentration of aerosol of the glycerol/propylene glycol mixture in the chamber with the animal. (2) Methods: In ex vivo studies, the lungs of Wistar rats are placed in the e-liquid for 1 h. For in vivo studies, Wistar rats were exposed to the e-liquid vapor in an aerosol administration chamber. After that, lung tissue samples were examined ex vivo using optical coherence tomography (OCT) and spectrometry with an integrating sphere. Absorption and reduced scattering coefficients were estimated for the control and experimental groups. Histological sections were made according to the standard protocol, followed by hematoxylin and eosin staining. (3) Results: Exposure to e-liquid in ex vivo and aerosol in in vivo studies was found to result in the optical clearing of lung tissue. Histological examination of the lung samples showed areas of emphysematous expansion of the alveoli, thickening of the alveolar septa, and the phenomenon of plasma permeation, which is less pronounced in in vivo studies than for the exposure of e-liquid ex vivo. E-liquid aerosol application allows for an increased resolution and improved imaging of lung tissues using OCT. Spectral studies showed significant differences between the control group and the ex vivo group in the spectral range of water absorption. It can be associated with dehydration of lung tissue owing to the hyperosmotic properties of glycerol and propylene glycol, which are the main components of e-liquids. (4) Conclusions: A decrease in the volume of air in lung tissue and higher packing of its structure under e-liquid vaping causes a better contrast of OCT images compared to intact lung tissue.

Ex vivo porcine lung immersed in e-liquid was investigated in-depth using confocal Raman micro-spectroscopy to assess the e-liquid influence on the lung. It was found that lung-related Raman band intensities at 1002, 1548, 1618 and 1655 cm -1 increased after first and second treatments except the surface, which was attributed to the well-known optical clearing (OC) effect due to alveoli filling with e-liquid resulting in light scattering reduction. The autofluorescence enhancement was explained by oxidative stress induced in lung during exposure to e-liquid. Moreover, e-liquid induced collagen dehydration was revealed by the I 937 /I 926 Raman band intensity ratio change. The effect was enhanced after the second treatment of the same lung tissue that indicates the possibility of multi-step OC treatment. We hypothesize that the nicotine-flavour-free e-liquids containing glycerol and propylene glycol could potentially be used in clinical protocols as OC agent for enhanced in-depth Raman-guided bronchoscopy., (© 2023 Wiley-VCH GmbH.)

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging., (© 2023. Springer Nature Limited.)

Significance: The clinical use of optical methods for in vivo skin imaging is limited by skin strong scattering properties, which reduce image contrast and probing depth. The efficiency of optical methods can be improved by optical clearing (OC). However, for the use of OC agents (OCAs) in a clinical setting, compliance with acceptable non-toxic concentrations is required., Aim: OC of in vivo human skin, combined with physical and chemical methods to enhance skin permeability to OCAs, was performed to determine the clearing-effectiveness of biocompatible OCAs using line-field confocal optical coherence tomography (LC-OCT) imaging., Approach: Nine types of OCAs mixtures were used in association with dermabrasion and sonophoresis for OC protocol on three volunteers hand skin. From 3D images obtained every 5 min for 40 min, the intensity and contrast parameters were extracted to assess their changes during the clearing process and evaluate each OCAs mixture's clearing efficacy., Results: The LC-OCT images average intensity and contrast increased over the entire skin depth with all OCAs. The best image contrast and intensity improvement was observed using the polyethylene glycol, oleic acid, and propylene glycol mixture., Conclusions: Complex OCAs featuring reduced component concentrations that meet drug regulation-established biocompatibility requirements were developed and proved to induce significant skin tissues clearing. By allowing deeper observations and higher contrast, such OCAs in combination with physical and chemical permeation enhancers may improve LC-OCT diagnostic efficacy., (© 2023 The Authors.)

This article describes a sapphire cryoprobe as a promising solution to the significant problem of modern cryosurgery that is the monitoring of tissue freezing. This probe consists of a sapphire rod manufactured by the edge-defined film-fed growth technique from Al 2 O 3 melt and optical fibers accommodated inside the rod and connected to the source and the detector. The probe's design enables detection of spatially resolved diffuse reflected intensities of tissue optical response, which are used for the estimation of tissue freezing depth. The current type of the 12.5-mm diameter sapphire probe cooled down by the liquid nitrogen assumes a superficial cryoablation. The experimental test made by using a gelatin-intralipid tissue phantom shows the feasibility of such concept, revealing the capabilities of monitoring the freezing depth up to 10 mm by the particular instrumentation realization of the probe. This justifies a potential of sapphire-based instruments aided by optical diagnosis in modern cryosurgery., (© 2022 Wiley-VCH GmbH.)

A fast calculation method was used to obtain the spectral optical properties of human normal and pathological (chromophobe renal cell carcinoma) kidney tissues. Using total transmittance, total reflectance and collimated transmittance spectra acquired from ex vivo kidney samples, the spectral optical properties of both tissues, namely the absorption, the scattering and the reduced scattering coefficients, as well as the scattering anisotropy, dispersion and light penetration depth, were calculated between 200 and 1000 nm. Analysis of the mean absorption coefficient spectra of the kidney tissues showed that both contain melanin and lipofuscin, and that 83 % of the melanin in the normal kidney converts into lipofuscin in the pathological kidney., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The method of immersion optical clearing reduces light scattering in tissues, which improves the use of optical technologies in the practice of clinicians. In this work, we studied the optical and molecular diffusion properties of cat ovarian tissues in the follicular (F-ph) and luteal (L-ph) phases under the influence of glycerol using reflectance spectroscopy in a broad wavelength range from 200 to 800 nm. It was found that the reflectance and transmittance of the ovaries are significantly lower in the range from 200 to 600 nm than for longer wavelengths from 600 to 800 nm, and the efficiency of optical clearing is much lower for the ovaries in the luteal phase compared to the follicular phase. For shorter wavelengths, the following tissue transparency windows were observed: centered at 350 nm and wide (46 ± 5) nm, centered at 500 nm and wide (25 ± 7) nm for the F-ph state and with a center of 500 nm and a width of (21 ± 6) nm for the L-ph state. Using the free diffusion model, Fick's law of molecular diffusion and the Bouguer-Beer-Lambert radiation attenuation law, the glycerol/tissue water diffusion coefficient was estimated as D = (1.9 ± 0.2)10 -6 cm 2 /s for ovaries at F-ph state and D = (2.4 ± 0.2)10 -6 cm 2 /s-in L-ph state, and the time of complete dehydration of ovarian samples, 0.8 mm thick, as 22.3 min in F-ph state and 17.7 min in L-ph state. The ability to determine the phase in which the ovaries are stated, follicular or luteal, is also important in cryopreservation, new reproductive technologies and ovarian implantation.

Adipose tissue (AT) optical properties for physiological temperatures and in vivo conditions are still insufficiently studied. The AT is composed mainly of packed cells close to spherical shape. It is a possible reason that AT demonstrates a very complicated spatial structure of reflected or transmitted light. It was shown with a cellular tissue phantom, is split into a fan of narrow tracks, originating from the insertion point and representing filament-like light distribution. The development of suitable approaches for describing light propagation in a AT is urgently needed. A mathematical model of the propagation of light through the layers of fat cells is proposed. It has been shown that the sharp local focusing of optical radiation (light localized near the shadow surface of the cells) and its cleavage by coupling whispering gallery modes depends on the optical thickness of the cell layer. The optical coherence tomography numerical simulation and experimental studies results demonstrate the importance of sharp local focusing in AT for understanding its optical properties for physiological conditions and at AT heating., (© 2023. The Author(s).)

The recent increasing interest in the application of radiology contrasting agents to create transparency in biological tissues implies that the diffusion properties of those agents need evaluation. The comparison of those properties with the ones obtained for other optical clearing agents allows to perform an optimized agent selection to create optimized transparency in clinical applications. In this study, the evaluation and comparison of the diffusion properties of gadobutrol and glycerol in skeletal muscle was made, showing that although gadobutrol has a higher molar mass than glycerol, its low viscosity allows for a faster diffusion in the muscle. The characterization of the tissue dehydration and refractive index matching mechanisms of optical clearing was made in skeletal muscle, namely by the estimation of the diffusion coefficients for water, glycerol and gadobutrol. The estimated tortuosity values of glycerol (2.2) and of gadobutrol (1.7) showed a longer path-length for glycerol in the muscle., (© 2022 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

The increase of tissue transparency through sequential optical immersion clearing treatments and treatment reversibility have high interest for clinical applications. To evaluate the clearing reversibility in a broad spectral range and the magnitude of the transparency created by a second treatment, the present study consisted on measuring the spectral collimated transmittance of lung tissues during a sequence of two treatments with electronic cigarette (e-cig) fluid, which was intercalated with an immersion in saline. The saline immersion clearly reverted the clearing effect in the lung tissue in the spectral range between 220 and 1000 nm. By a later application of a second treatment with the e-cig fluid, the magnitude of the optical clearing effect was observed to be about the double as the one observed in the first treatment, showing that the molecules of the optical clearing agent might have converted some bound water into mobile water during the first treatment., (© 2022 Wiley-VCH GmbH.)

A distinctive feature of this review is a critical analysis of methods and results of measurements of the optical properties of tissues in a wide spectral range from deep UV to terahertz waves. Much attention is paid to measurements of the refractive index of biological tissues and liquids, the knowledge of which is necessary for the effective application of many methods of optical imaging and diagnostics. The optical parameters of healthy and pathological tissues are presented, and the reasons for their differences are discussed, which is important for the discrimination of pathologies and the demarcation of their boundaries. When considering the interaction of terahertz radiation with tissues, the concept of an effective medium is discussed, and relaxation models of the effective optical properties of tissues are presented. Attention is drawn to the manifestation of the scattering properties of tissues in the THz range and the problems of measuring the optical properties of tissues in this range are discussed. In conclusion, a method for the dynamic analysis of the optical properties of tissues under optical clearing using an application of immersion agents is presented. The main mechanisms and technologies of optical clearing, as well as examples of the successful application for differentiation of healthy and pathological tissues, are analyzed., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Significance: Fluorescence molecular lifetime tomography (FMLT) plays an increasingly important role in experimental oncology. The article presents and experimentally verifies an original method of mesoscopic time domain FMLT, based on an asymptotic approximation to the fluorescence source function, which is valid for early arriving photons., Aim: The aim was to justify the efficiency of the method by experimental scanning and reconstruction of a phantom with a fluorophore. The experimental facility included the TCSPC system, the pulsed supercontinuum Fianium laser, and a three-channel fiber probe. Phantom scanning was done in mesoscopic regime for three-dimensional (3D) reflectance geometry., Approach: The sensitivity functions were simulated with a Monte Carlo method. A compressed-sensing-like reconstruction algorithm was used to solve the inverse problem for the fluorescence parameter distribution function, which included the fluorophore absorption coefficient and fluorescence lifetime distributions. The distributions were separated directly in the time domain with the QR-factorization least square method., Results: 3D tomograms of fluorescence parameters were obtained and analyzed using two strategies for the formation of measurement data arrays and sensitivity matrices. An algorithm is developed for the flexible choice of optimal strategy in view of attaining better reconstruction quality. Variants on how to improve the method are proposed, specifically, through stepped extraction and further use of a posteriori information about the object., Conclusions: Even if measurement data are limited, the proposed method is capable of giving adequate reconstructions but their quality depends on available a priori (or a posteriori ) information. Further research aims to improve the method by implementing the variants proposed., (© 2022 The Authors.)

Dura mater (DM) is a connective tissue with dense collagen, which is a protective membrane surrounding the human brain. The optical clearing (OC) method was used to make DM more transparent, thereby allowing to increase in-depth investigation by confocal Raman micro-spectroscopy and estimate the diffusivity of 50% glycerol and water migration. Glycerol concentration was obtained, and the diffusion coefficient was calculated, which ranged from 9.6 × 10 -6 to 3.0 × 10 -5 cm 2 /s. Collagen-related Raman band intensities were significantly increased for all depths from 50 to 200 µm after treatment. In addition, the changes in water content during OC showed that 50% glycerol induces tissue dehydration. Weakly and strongly bound water types were found to be most concentrated, playing a major role in the glycerol-induced water flux and OC. Results show that OC is an efficient method for controlling the DM optical properties, thereby enhancing the in-depth probing for laser therapy and diagnostics of the brain. DM is a comparable to various collagen-containing tissues and organs, such as sclera of eyes and skin dermis.

Infectious diseases are among the most severe threats to modern society. Current methods of virus infection detection based on genome tests need reagents and specialized laboratories. The desired characteristics of new virus detection methods are noninvasiveness, simplicity of implementation, real-time, low cost and label-free detection. There are two groups of methods for molecular biomarkers' detection and analysis: (i) a sample physical separation into individual molecular components and their identification, and (ii) sample content analysis by laser spectroscopy. Variations in the spectral data are typically minor. It requires the use of sophisticated analytical methods like machine learning. This review examines the current technological level of laser spectroscopy and machine learning methods in applications for virus infection detection., (© 2022 Wiley-VCH GmbH.)

In this paper, the measurement and modeling of optical properties in the terahertz (THz) range of adipose tissue and its components with temperature changes were performed. Spectral measurements were made in the frequency range 0.25-1 THz. The structural models of main triglycerides of fatty acids are constructed using the B3LYP/6-31G(d) method and the Gaussian03, Revision B.03 program. The optical density (OD) of adipose tissue samples decreases as temperature increases, which can be associated mostly with the dehydration of the sample. Some inclusion of THz wave scattering suppression into the OD decrease can also be expected due to refractive index matching provided by free fatty acids released from adipocytes at thermally induced cell lipolysis. It was shown that the difference between the THz absorption spectra of water and fat makes it possible to estimate the water content in adipose tissue. The proposed model was verified on the basis of molecular modeling and a comparison with experimental data for terahertz spectra of adipose tissue during its heating. Knowing the exact percentage of free and bound water in adipose tissue can help diagnose and monitor diseases, such as diabetes, obesity, and cancer.

Optical clearing of the lung tissue aims to make it more transparent to light by minimizing light scattering, thus allowing reconstruction of the three-dimensional structure of the tissue with a much better resolution. This is of great importance for monitoring of viral infection impact on the alveolar structure of the tissue and oxygen transport. Optical clearing agents (OCAs) can provide not only lesser light scattering of tissue components but also may influence the molecular transport function of the alveolar membrane. Air-filled lungs present significant challenges for optical imaging including optical coherence tomography (OCT), confocal and two-photon microscopy, and Raman spectroscopy, because of the large refractive-index mismatch between alveoli walls and the enclosed air-filled region. During OCT imaging, the light is strongly backscattered at each air-tissue interface, such that image reconstruction is typically limited to a single alveolus. At the same time, the filling of these cavities with an OCA, to which water (physiological solution) can also be attributed since its refractive index is much higher than that of air will lead to much better tissue optical transmittance. This review presents general principles and advances in the field of tissue optical clearing (TOC) technology, OCA delivery mechanisms in lung tissue, studies of the impact of microbial and viral infections on tissue response, and antimicrobial and antiviral photodynamic therapies using methylene blue (MB) and indocyanine green (ICG) dyes as photosensitizers., Competing Interests: Conflict of interestsAll authors declare that they have no conflicts of interest., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The accurate estimation of skin and skull optical properties over a wide wavelength range of laser radiation has great importance in optogenetics and other related applications. In the present work, using the Kubelka-Munk model, finite-element solution of the diffusion equation, inverse adding-doubling (IAD), and Monte-Carlo simulation, we estimated the refractive index, absorption and scattering coefficients, penetration depth, and the optical fluence distribution in rabbit head tissues ex vivo, after dividing the heads into three types of tissues with an average thickness of skin of 1.1 mm, skull of 1 mm, and brain of 3 mm. The total diffuse reflectance and transmittance were measured using a single integrating sphere optical setup for laser radiation of 532, 660, 785, and 980 nm. The calculated optical properties were then applied to the diffusion equation to compute the optical fluence rate distribution at the boundary of the samples using the finite element method. Monte-Carlo simulation was implemented for estimating the optical fluence distribution through a model containing the three tissue layers. The scattering coefficient decreased at longer wavelengths, leading to an increase in optical fluence inside the tissue samples, indicating a higher penetration depth, especially at 980 nm. In general, the obtained results show good agreement with relevant literature.

Light absorption and scattering in biological tissue are significant variables in optical imaging technologies and regulating them enhances optical imaging quality. Optical clearing methods can decrease light scattering and improve optical imaging quality to some extent but owing to their limited efficacy and the potential influence of optical clearing agents on tissue functioning, complementing approaches must be investigated. In this paper, a new strategy of optical clearing proposed as time-dependent or temporal tissue optical clearing (TTOC) is described. The absorption and scattering in light interaction with tissue are regulated in the TTOC technique by altering the pulse width. Here, the dependence of optical properties of matter on the pulse width in a gelatin-based phantom was investigated experimentally. Then, a semi-classical model was introduced to computationally study of Ultra-short laser/matter interaction. After studying phantom, the absorption and scattering probabilities in the interaction of the pulse with modeled human skin tissue were investigated using the proposed model for pulse widths ranging from 1µs to 10fs. The propagation of the pulse through the skin tissue was simulated using the Monte Carlo technique by computing the pulse width-dependent optical properties (absorption coefficient µ a , scattering coefficient µ s , and anisotropy factor g). Finally, the penetration depth of light into the tissue and reflectance for different pulse widths was found., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Optical clearing (OC) of adipose tissue has not been studied enough, although it can be promising in medical applications, including surgery and cosmetology, for example, to visualize blood vessels or increase the permeability of tissues to laser beams. The main objective of this work is to develop technology for OC of abdominal adipose tissue in vivo using hyperosmotic optical clearing agents (OCAs). The maximum OC effect (77%) was observed for ex vivo rat adipose tissue samples exposed to OCA on fructose basis for 90 minutes. For in vivo studies, the maximum effect of OC (65%) was observed when using OCA based on diatrizoic acid and dimethylsulfoxide for 120 minutes. Histological analysis showed that in vivo application of OCAs may induce a limited local necrosis of fat cells. The efficiency of OC correlated with local tissue damage through cell necrosis due to accompanied cell lipolysis., (© 2022 Wiley-VCH GmbH.)

Multimodality registration of optical and MR images in the same tissue volume in vivo may be enabled by MR contrast agents with an optical clearing (OC) effect. The goals of this study were to (a) investigate the effects of clinical MR contrast agent gadobutrol (GB) and its combinations as a potential OC agent assisting in fluorescence intensity (FI) imaging in vivo and (b) evaluate MRI as a tool for imaging of topical or systemic application of GB for the purpose of OC. Subcutaneous tumor xenografts expressing red fluorescent marker protein were used as disease models. MRI was performed at 1 T 1 H MRI using T 1 -weighted 3D gradient-echo (T1w-3D GRE) sequences to measure time-dependent MR signal intensity changes by region of interest analysis after image segmentation. Topical application of 1.0 M or 0.7 M GB-containing OC mixture with water and dimethyl sulfoxide showed similar 30-40% increases of tumor FI during the initial 15 min. Afterwards, the OC effect of GB on FI and tumor/background FI ratio showed a decrease over time in the case of 1.0 M GB, unlike the 0.7 M GB mixture, which resulted in a steady increase of FI and tumor/background ratio for 15-60 min. The use of T1w-3D GRE MR pulse sequences showed that concentrated 1.0 M GB resulted in MR signal loss of the skin due to high magnetic susceptibility and that signal loss coincided with the OC effect. Intravenous injection of 0.3 mmol GB/kg resulted in a rapid but transient 40% increase of FI of the tumors. Overall, 1 T MRI enabled tracking of GB-containing OC compositions on the skin surface and tumor tissue, supporting the observation of a time-dependent FI increase in vivo., (© 2022 John Wiley & Sons, Ltd.)

The main goal of this work was to modify the previously developed blade-type planar structure using plasmonic gold nanostars in order to stimulate photofield emission and provide efficient laser control of the electron current. Localization and enhancement of the field at the tips of gold nanostars provided a significant increase in the tunneling electron current in the experimental sample (both electrical field and photofield emission). Irradiation at a wavelength in the vicinity of the plasmon resonance (red laser) provided a gain in the photoresponse value of up to 5 times compared to irradiation far from the resonance (green laser). The prospects for transition to regimes of structure irradiation by femtosecond laser pulses at the wavelength of surface plasmon resonance, which lead to an increase in the local optical field, are discussed. The kinetics of the energy density of photoinduced hot and thermalized electrons is estimated. The proposed laser-controlled matrix current source is promising for use in X-ray computed tomography systems.

The effect of tissue optical clearing (TOC) to increase the probing depth and observe in-depth structure of the ex vivo porcine dura mater was studied by confocal Raman microspectroscopy (CRM). Raman intensities were significantly increased at the depth of 250 μm for all collagen bands after treatment with glycerol. The influence of glycerol on collagen hydration was also investigated. The results indicate that the process of TOC can be divided into three main steps. The first one is a fast process of tissue dehydration accompanied by collagen shrinkage while the second relatively slow process is related to the glycerol penetration into the interfibrillar space of collagen combined with swelling of tissue. The third step is collagen dissociation caused by the high concentration of glycerol. To the best of our knowledge, this study is the first example to introduce the TOC technique in assisting CRM of ex vivo dura mater in-depth probing., (© 2021 Wiley-VCH GmbH.)

Objectives: The development of compact diagnostic probes and instruments with an ability to direct access to organs and tissues and integration of these instruments into surgical workflows is an important task of modern physics and medicine. The need for such tools is essential for surgical oncology, where intraoperative visualization and demarcation of tumor margins define further prognosis and survival of patients. In this paper, the possible solution for this intraoperative imaging problem is proposed and its feasibility to detect tumorous tissue is studied experimentally., Methods: For this aim, the sapphire scalpel was developed and fabricated using the edge-defined film-fed growth technique aided by mechanical grinding, polishing, and chemical sharpening of the cutting edge. It possesses optical transparency, mechanical strength, chemical inertness, and thermal resistance alongside the presence of the as-grown hollow capillary channels in its volume for accommodating optical fibers. The rounding of the cutting edge exceeds the same for metal scalpels and can be as small as 110 nm. Thanks to these features, sapphire scalpel combines tissue dissection with light delivering and optical diagnosis. The feasibility for the tumor margin detection was studied, including both gelatin-based tissue phantoms and ex vivo freshly excised specimens of the basal cell carcinoma from humans and the glioma model 101.8 from rats. These tumors are commonly diagnosed either non-invasively or intraoperatively using different modalities of fluorescence spectroscopy and imaging, which makes them ideal candidates for our feasibility test. For this purpose, fiber-based spectroscopic measurements of the backscattered laser radiation and the fluorescence signals were carried out in the visible range., Results: Experimental studies show the feasibility of the proposed sapphire scalpel to provide a 2-mm-resolution of the tumor margins' detection, along with an ability to distinguish the tumor invasion region, which results from analysis of the backscattered optical fields and the endogenous or exogenous fluorescence data., Conclusions: Our findings justified a strong potential of the sapphire scalpel for surgical oncology. However, further research and engineering efforts are required to optimize the sapphire scalpel geometry and the optical diagnosis protocols to meet the requirements of oncosurgery, including diagnosis and resection of neoplasms with different localizations and nosologies., (© 2021 Wiley Periodicals LLC.)