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.

Dynamic Light Scattering in Biomedical Applications: feature issue introduction.

The feature Issue on "Dynamic Light Scattering in Biomedical Applications" presents a compilation of research breakthroughs and technological advancements that have shaped the field of biophotonics, particularly in the non-invasive exploration of biological tissues. Highlighting the significance of dynamic light scattering (DLS) alongside techniques like laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), and laser speckle contrast imaging (LSCI), this issue underscores the versatile applications of these methods in capturing the intricate dynamics of microcirculatory blood flow across various tissues. Contributions explore developments in fluorescence tomography, the integration of machine learning for data processing, enhancements in microscopy for cancer detection, and novel approaches in optical biophysics, among others. Innovations featured include a high-resolution speckle contrast tomography system for deep blood flow imaging, a rapid estimation technique for real-time tissue perfusion imaging, and the use of convolutional neural networks for efficient blood flow mapping. Additionally, studies delve into the impact of skin strain on spectral reflectance, the sensitivity of cerebral blood flow measurement techniques, and the potential of photobiomodulation for enhancing brain function. This issue not only showcases the latest theoretical and experimental strides in DLS-based imaging but also anticipates the continued evolution of these modalities for groundbreaking applications in disease detection, diagnosis, and monitoring, marking a pivotal contribution to the field of biomedical optics.

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.

Real-time laser speckle contrast imaging for intraoperative neurovascular blood flow assessment: animal experimental study.

The use of various blood flow control methods in neurovascular interventions is crucial for reducing postoperative complications. Neurosurgeons worldwide use different methods, such as contact Dopplerography, intraoperative indocyanine videoangiography (ICG) video angiography, fluorescein angiography, flowmetry, intraoperative angiography, and direct angiography. However, there is no noninvasive method that can assess the presence of blood flow in the vessels of the brain without the introduction of fluorescent substances throughout the intervention. The real-time laser-speckle contrast imaging (LSCI) method was studied for its effectiveness in controlling blood flow in standard cerebrovascular surgery cases in rat common carotid arteries, such as proximal occlusion, trapping, reperfusion, anastomosis, and intraoperative vessel thrombosis. The real-time LSCI method is a promising method for use in neurosurgical practice. This approach allows timely diagnosis of intraoperative disturbance of blood flow in vessels in cases of clip occlusion or thrombosis. Additionally, LSCI allows us to reliably confirm the functioning of the anastomosis and reperfusion after removal of the clips and thrombolysis in real time. An unresolved limitation of the method is noise from movements, but this does not reduce the value of the method. Additional research is required to improve the quality of the data obtained.

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.

Closest horizons of Hsp70 engagement to manage neurodegeneration.

Our review seeks to elucidate the current state-of-the-art in studies of 70-kilodalton-weighed heat shock proteins (Hsp70) in neurodegenerative diseases (NDs). The family has already been shown to play a crucial role in pathological aggregation for a wide spectrum of brain pathologies. However, a slender boundary between a big body of fundamental data and its implementation has only recently been crossed. Currently, we are witnessing an anticipated advancement in the domain with dozens of studies published every month. In this review, we briefly summarize scattered results regarding the role of Hsp70 in the most common NDs including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We also bridge translational studies and clinical trials to portray the output for medical practice. Available options to regulate Hsp70 activity in NDs are outlined, too.

A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption.

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.

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.

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.

Laser Speckle Contrast Imaging in Neurosurgery: A Systematic Review.

BACKGROUND: Intraoperative study of blood flow in the brain vessels is among the most critical topics of modern neurosurgery. One of the promising methods for intraoperative monitoring of blood flow is laser speckle contrast imaging (LSCI). This systematic review aims to analyze the experience of using intraoperative LSCI in neurosurgical interventions. METHODS: The literature search was carried out in the PubMed and Web of Science databases using the keywords "Laser-Speckle," "Laser Speckle," "Laser speckle contrast imaging," and "LSCI." We allowed the search to include the following criteria: 1) publication in the English language, 2) full access to the article, 3) information about the method of treatment, and 4) the results presented for at least one patient. RESULTS: The initial search resulted in the detection of 508 publications, of which 476 were eliminated during the initial assessment of titles and abstracts. Two more articles were excluded due to the lack of data in the English language. Twenty articles were found to be focused on nonhuman studies and therefore were excluded. In three more studies treatment of non-neurosurgical patients was reported. The final analysis included 8 articles with 102 patients overall. CONCLUSIONS: LSCI is a promising intraoperative method for intraoperative cerebral blood flow assessing. This method offers several advantages over other modalities. The experience of use is limited to a small number of case series. Further investigation of the method and its implementation in clinical practice is needed.

Structural changes of erythrocyte membrane revealed by 3D confocal optical profilometer.

We examined hematological changes influenced by the experimental hypervitaminosis A. The 3D confocal optical profilometer was applied for assessment of the erythrocytes' membrane structural changes influenced by an overdose of vitamin A. The blood smears were evaluated in terms of alterations of geometrical and optical parameters of erythrocytes for two groups of animals: oil base and retinol palmitate (n = 9 animals for each group). The results demonstrate that an overdose of retinol palmitate causes changes in the torus curvature and pallor of discocytes, their surface area and volume. The observed structural malformations of the shape of red blood cells become visible at the earlier preclinical stage of changes in animal state and behavior. With this in mind, the results of the study open a new area of research in the certain dysfunction diagnosis of red blood cells and have a great potential in the further development of new curative protocols.

The number of the intraepithelial T cells correlate with the proliferation index in human bulbourethral gland epithelium.

Background: Our study has immunohistochemically examined T cells localization and number as well as proliferative activity level for the bulbourethral gland epithelium in men of different ages, using monoclonal antibodies against CD45RO and proliferating cell nuclear antigen (PCNA). Results: We have found that the T cells have been localized mainly in excretory ducts epithelium of the glands in any age group, meanwhile their relative number varies with age. The excretory ducts epithelium has shown a high proliferative activity when in acini the PCNA index has been low. Postnatal dynamics of the epithelium proliferative activity positively correlates with age-related density fluctuations in lymphocytic infiltration of the glands. Conclusions: We consider that intraepithelial T cells may contribute to the regulation of epithelial cells proliferation in the bulbourethral glands.

A combined use of silver pretreatment and impregnation with consequent Nissl staining for cortex and striatum architectonics study.

Despite a rapid growth in the application of modern techniques for visualization studies in life sciences, the classical methods of histological examination are yet to be outdated. Herein, we introduce a new approach that involves combining silver nitrate pretreatment and impregnation with consequent Nissl (cresyl violet) staining for cortex and striatum architectonics study on the same microscopy slide. The developed approach of hybrid staining provides a high-quality visualization of cellular and subcellular structures, including impregnated neurons (about 10%), Nissl-stained neurons (all the remaining ones), and astrocytes, as well as chromatophilic substances, nucleoli, and neuropil in paraffin sections. We provide a comparative study of the neuronal architectonics in both the motor cortex and striatum based on the differences in their tinctorial properties. In addition to a comparative study of the neuronal architectonics in both the motor cortex and striatum, the traditional methods to stain the cortex (motor and piriform) and the striatum are considered. The proposed staining approach compiles the routine conventional methods for thin sections, expanding avenues for more advanced examination of neurons, blood-brain barrier components, and fibers both under normal and pathological conditions. One of the main hallmarks of our method is the ability to detect changes in the number of glial cells. The results of astrocyte visualization in the motor cortex obtained by the developed technique agree well with the alternative studies by glial fibrillary acidic protein (GFAP) immunohistochemical reaction. The presented approach of combined staining has great potential in current histological practice, in particular for the evaluation of several neurological disorders in clinical, pre-clinical, or neurobiological animal studies.

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.