Polarization enhancement mechanism from tissue staining in multispectral Mueller matrix microscopy.

Mueller matrix microscopy can provide comprehensive polarization-related optical and structural information of biomedical samples label-freely. Thus, it is regarded as an emerging powerful tool for pathological diagnosis. However, the staining dyes have different optical properties and staining mechanisms, which can put influence on Mueller matrix microscopic measurement. In this Letter, we quantitatively analyze the polarization enhancement mechanism from hematoxylin and eosin (H&E) staining in multispectral Mueller matrix microscopy. We examine the influence of hematoxylin and eosin dyes on Mueller matrix-derived polarization characteristics of fibrous tissue structures. Combined with Monte Carlo simulations, we explain how the dyes enhance diattenuation and linear retardance as the illumination wavelength changed. In addition, it is demonstrated that by choosing an appropriate incident wavelength, more visual Mueller matrix polarimetric information can be observed of the H&E stained tissue sample. The findings can lay the foundation for the future Mueller matrix-assisted digital pathology.

Polarization feature fusion and calculation of birefringence dynamics in complex anisotropic media.

As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.

Polarization Characterization of Porous Particles Based on DDA Simulation and Multi-Angle Polarization Measurements.

Porous suspended particles are hazardous to human health due to their strong absorption capacity for toxic substances. A fast, accurate, in situ and high-throughput method to characterize the microporous structure of porous particles has extensive application value. The polarization changes during the light scattering of aerosol particles are highly sensitive to their microstructural properties, such as pore size and porosity. In this study, we propose an overlapping sphere model based on the discrete dipole approximation (DDA) to calculate the polarization scattering characteristics of porous particles. By combining scattering calculations with multi-dimensional polarization indexes measured by a multi-angle polarized scattering vector detection system, we achieve the identification and classification of pore-type components in suspended particles. The maximum deviation based on multiple indexes is less than 0.16% for the proportion analysis of mixed particles. Simultaneously, we develop a quantitative inversion algorithm on pore size and porosity. The inversion results of the three porous polymer particles support the validity and feasibility of our method, where the inversion error of partial particles is less than 4% for pore size and less than 6% for porosity. The study demonstrates the potential of polarization measurements and index systems applied in characterizing the micropore structure of suspended particles.

Complex Spatial Illumination Scheme Optimization of Backscattering Mueller Matrix Polarimetry for Tissue Imaging and Biosensing.

Polarization imaging and sensing techniques have shown great potential for biomedical and clinical applications. As a novel optical biosensing technology, Mueller matrix polarimetry can provide abundant microstructural information of tissue samples. However, polarimetric aberrations, which lead to inaccurate characterization of polarization properties, can be induced by uneven biomedical sample surfaces while measuring Mueller matrices with complex spatial illuminations. In this study, we analyze the detailed features of complex spatial illumination-induced aberrations by measuring the backscattering Mueller matrices of experimental phantom and tissue samples. We obtain the aberrations under different spatial illumination schemes in Mueller matrix imaging. Furthermore, we give the corresponding suggestions for selecting appropriate illumination schemes to extract specific polarization properties, and then provide strategies to alleviate polarimetric aberrations by adjusting the incident and detection angles in Mueller matrix imaging. The optimized scheme gives critical criteria for the spatial illumination scheme selection of non-collinear backscattering Mueller matrix measurements, which can be helpful for the further development of quantitative tissue polarimetric imaging and biosensing.

Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity.

PURPOSE: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. METHODS: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). RESULTS: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). CONCLUSIONS: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1ß)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

Monolithic Integration of GaN-Based Transistors and Micro-LED.

Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit. Researchers take advantage of the high performance of the transistors to achieve low power consumption, high current gain, and fast response frequency. This paper gives a review of recent studies on the new integration methods of micro-LEDs with different types of transistors, including the integration with BJT, HEMT, TFT, and MOSFET.

A Cyclical Magneto-Responsive Massage Dressing for Wound Healing.

Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.

Discrepancy of coordinate system selection in backscattering Mueller matrix polarimetry: exploring photon coordinate system transformation invariants.

In biomedical studies, Mueller matrix polarimetry is gaining increasing attention because it can comprehensively characterize polarization-related vectorial properties of the sample, which are crucial for microstructural identification and evaluation. For backscattering Mueller matrix polarimetry, there are two photon coordinate selection conventions, which can affect the following Mueller matrix parameters calculation and information acquisition quantitatively. In this study, we systematically analyze the influence of photon coordinate system selection on the backscattering Mueller matrix polarimetry. We compare the Mueller matrix elements in the right-handed-nonunitary and non-right-handed-unitary coordinate systems, and specifically deduce the changes of Mueller matrix polar decomposition, Mueller matrix Cloude decomposition and Mueller matrix transformation parameters widely used in backscattering Mueller matrix imaging as the photon coordinate system varied. Based on the theoretical analysis and phantom experiments, we provide a group of photon coordinate system transformation invariants for backscattering Mueller matrix polarimetry. The findings presented in this study give a crucial criterion of parameters selection for backscattering Mueller matrix imaging under different photon coordinate systems.

Analysis and optimization of aberration induced by oblique incidence for in-vivo tissue polarimetry.

For in-vivo polarimetry such as Mueller matrix endoscopy of human internal organ cavities, the complicated undulating tissue surfaces deliver an inescapable occurrence of oblique incidence, which induce a prominent aberration to backscattering tissue polarimetry. In this Letter, we quantitatively analyze such polarimetric aberration on polarization basic parameters derived from the Mueller matrix. A correlation heatmap is obtained as applicable criteria to select an appropriate incident angle for different polarization basic parameters. Based on the analyzing results, we propose two aberration optimization strategies of parameter selection and azimuth rotation, which are suitable for tissue samples with randomly and well-aligned fiber textures, respectively. Both strategies are demonstrated to be effective in the ex-vivo human gastric muscularis tissue experiment. The findings presented in this Letter can be useful to provide accurate polarization imaging results, widely applied on in-vivo polarimetric endoscopy for tissues with complicated surface topography.

Influence of hematoxylin and eosin staining on linear birefringence measurement of fibrous tissue structures in polarization microscopy.

Significance: For microscopic polarization imaging of tissue slices, two types of samples are often prepared: one unstained tissue section for polarization imaging to avoid possible influence from staining dyes quantitatively and one hematoxylin-eosin (H&E) stained adjacent tissue section for histological diagnosis and structural feature identification. However, this sample preparation strategy requires high-quality adjacent tissue sections, and labeling the structural features on unstained tissue sections is impossible. With the fast development of data driven-based polarimetric analysis, which requires a large amount of pixel labeled images, a possible method is to directly use H&E stained slices, which are standard samples archived in clinical hospitals for polarization measurement. Aim: We aim to study the influence of hematoxylin and eosin staining on the linear birefringence measurement of fibrous tissue structures. Approach: We examine the linear birefringence properties of four pieces of adjacent bone tissue slices with abundant collagen fibers that are unstained, H&E stained, hematoxylin (H) stained, and eosin (E) stained. After obtaining the spatial maps of linear retardance values for the four tissue samples, we carry out a comparative study using a frequency distribution histogram and similarity analysis based on the Bhattacharyya coefficient to investigate how H&E staining affects the linear birefringence measurement of bone tissues. Results: Linear retardance increased after H&E, H, or E staining (41.7%, 40.8%, and 72.5% increase, respectively). However, there is no significant change in the imaging contrast of linear retardance in bone tissues. Conclusions: The linear retardance values induced by birefringent collagen fibers can be enhanced after H&E, H, or E staining. However, the structural imaging contrasts based on linear retardance did not change significantly or the staining did not generate linear birefringence on the sample area without collagen. Therefore, it can be acceptable to prepare H&E stained slices for clinical applications of polarimetry based on such a mapping relationship.

Analyzing the influence of oblique incidence on quantitative backscattering tissue polarimetry: a pilot ex vivo study.

Significance: Among the available polarimetric techniques, backscattering Mueller matrix (MM) polarimetry provides a promising non-contact and quantitative tool for in vivo tissue detection and clinical diagnosis. To eliminate the surface reflection from the sample cost-effectively, the non-collinear backscattering MM imaging setup always has an oblique incidence. Meanwhile, for practical organ cavities imaged using polarimetric gastrointestinal endoscopy, the uneven tissue surfaces can induce various relative oblique incidences inevitably, which can affect the polarimetry in a complicated manner and needs to be considered for detailed study. Aim: The purpose of this study is to systematically analyze the influence of oblique incidence on backscattering tissue polarimetry. Approach: We measured the MMs of experimental phantom and ex vivo tissues with different incident angles and adopted a Monte Carlo simulation program based on cylindrical scattering model for further verification and analysis. Meanwhile, the results were quantitatively evaluated using the Fourier transform, basic statistics, and frequency distribution histograms. Results: Oblique incidence can induce different changes on non-periodic, two-periodic, and four-periodic MM elements, leading to false-positive and false-negative polarization information for tissue polarimetry. Moreover, a prominent oblique incidence can bring more dramatic signal variations, such as phase retardance and element transposition. Conclusions: The findings presented in this study give some crucial criterions of appropriate incident angle selections for in vivo polarimetric endoscopy and other applications and can also be valuable references for studying how to minimize the influence further.

Twelve-year outcomes of bedside laser photocoagulation for severe retinopathy of prematurity.

Purpose: The purpose of this study is to evaluate the 12-year outcomes of bedside laser photocoagulation (LP) for severe retinopathy of prematurity (ROP) under sedation combined with ocular surface anesthesia in neonatal intensive care units (NICU). Design: The study is a retrospective case series. Methods: Infants treated with bedside LP for severe ROP from April 2009 to September 2021 were included. All LP treatments were performed under sedation and surface anesthesia at the bedside in NICU. Data were recorded for clinical and demographic characteristics, total laser spots, duration of treatment, proportion of total regression of ROP, proportion of recurrence, and adverse events. Results: A total of 364 infants (715 eyes) were included, with a mean gestational age of 28.6 ± 2.4 weeks (range: 22.6-36.6 weeks) and a mean birth weight of 1,156.0 ± 339.0 g (range: 480-2,200 g). The mean number of laser spots was 832 ± 469, and the mean duration of treatment was 23.5 ± 5.3 min per eye. Of all the eyes, 98.3% responded to LP with complete regression of ROP. ROP recurred in 15 (2.1%) eyes after the initial LP. Additional LP was performed in seven (1.0%) eyes. No patient exhibited mistaken LP of other ocular tissues, and there were no serious ocular adverse effects. None of them needed endotracheal intubation. Conclusions: Bedside LP treatment is effective and safe for premature infants with severe ROP under sedation and surface anesthesia in NICU, especially for infants whose general condition is unstable and not suitable for transport.

Regioselective Deuteration of Arenes Enabled by Simple Heterogeneous Palladium Catalysis.

A heterogeneous redox-neutral palladium-catalytic platform was reported for the preparation of deuterated (hetero) arenes from (hetero) arenes mediated by regioselective C(sp2)-H thianthrenation utilizing commercially available and recyclable Pd/C catalyst. A wide range of deuterated compounds could be obtained in high yields with excellent levels of deuterium incorporation under these simple heterogeneous catalytic conditions with the requirement of stable and easily handled DCOONa as a deuterium source. The late-stage deuteration of pharmaceuticals and bioactive molecules was also achieved by this approach.

3D Prestress Bioprinting of Directed Tissues.

Many mammalian tissues adopt a specific cellular arrangement under stress stimulus that enables their unique function. However, conventional 3D encapsulation often fails to recapitulate the complexities of these arrangements, thus motivating the need for advanced cellular arrangement approaches. Here, an original 3D prestress bioprinting approach of directed tissues under the synergistic effect of static sustained tensile stress and molecular chain orientation, with an aid of slow crosslinking in bioink, is developed. The semi-crosslinking state of the designed bioink exhibits excellent elasticity for applying stress on the cells during the sewing-like process. After bioprinting, the bioink gradually forms complete crosslinking and keeps the applied stress force to induce cell-orientated growth. More importantly, multiple cell types can be arranged directionally by this approach, while the internal stress of the hydrogel filament is also adjustable. In addition, compared with conventional bioprinted skin, the 3D prestress bioprinted skin results in a better wound healing effect due to promoting the angiogenesis of granulation tissue. This study provides a prospective strategy to engineer skeletal muscles, as well as tendons, ligaments, vascular networks, or combinations thereof in the future.

A Dual-Modality Imaging Method Based on Polarimetry and Second Harmonic Generation for Characterization and Evaluation of Skin Tissue Structures.

The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens' images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin.

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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23 (FGF23) by tumor tissue. We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism. The patient's symptoms did not improve after removal of the tumor from the hyoid body, and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland. TIO derived from the tongue tumor is very rare, and also subsequent tertiary hyperparathyroidism is even rarer. This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.

Clinical and genetic characteristics for 4 patients with Type Ib pseudohypoparathyroidism. / 4例Ibåž‹å‡æ€§ç”²çŠ¶æ—è ºåŠŸèƒ½å‡é€€ç—‡çš„ä¸´åºŠå’Œé—ä¼ å­¦ç‰¹å¾.

Pseudohypoparayhyroidism (PHP) is a rare autosomal dominant or recessive genetic disorder characterized by low calcium, high phosphorus, and target organ resistance to parathyroid. The clinical characteristics and genetic features in 4 patients with Type Ib PHP in the Third Xiangya Hospital, Central South University, have been reviewed. All 4 patients had low calcium, high phosphorus, and parathyroid resistance. Among them, 2 patients had slightly elevated thyroid stimulating hormone and mild features of Albright's hereditary osteodystrophy, and one patient had hypokalemia. No guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1 (GNAS) and gene variant associated with hypokalemia were identified using the whole exome sequencing. The results of the methylation-specific multiple ligation-dependent probe amplification showed that there were abnormal methylation of the upstream differentially methylated regions of GNAS in the 4 patients. There were phenotype overlap among the various subtypes of PHP. Detection of GNAS gene methylation in patients with clinical suspicion of Type Ib PHP is helpful for the diagnosis and treatment of PHP.

A Smartphone-Based Biosensor for Non-Invasive Monitoring of Total Hemoglobin Concentration in Humans with High Accuracy.

In this paper, we propose a smartphone-based biosensor for detecting human total hemoglobin concentration in vivo with high accuracy. Compared to the existing biosensors used to measure hemoglobin concentration, the smartphone-based sensor utilizes the camera, memory, and computing power of the phone. Thus, the cost is largely reduced. Compared to existing smartphone-based sensors, we developed a highly integrated multi-wavelength LED module and a specially designed phone fixture to reduce spatial errors and motion artifacts, respectively. In addition, we embedded a new algorithm into our smartphone-based sensor to improve the measurement accuracy; an L*a*b* color space transformation and the "a" parameter were used to perform the final quantification. We collected 24 blood samples from normal and anemic populations. The adjusted R2 of the prediction results obtained from the multiple linear regression method reached 0.880, and the RMSE reached 9.04, which met the accuracy requirements of non-invasive detection of hemoglobin concentration.