Vectorial inverse scattering for dielectric tensor tomography: overcoming challenges of reconstruction of highly scattering birefringent samples.

Many important microscopy samples, such as liquid crystals, biological tissue, or starches, are birefringent in nature. They scatter light differently depending on the polarization of the light and the orientation of the molecules. The complete characterization of a birefringent sample is a challenging task because its 3 × 3 dielectric tensor must be reconstructed at every three-dimensional position. Moreover, obtaining a birefringent tomogram is more arduous for thick samples, where multiple light scattering should also be considered. In this study, we developed a new dielectric tensor tomography algorithm that enables full characterization of highly scattering birefringent samples by solving the vectoral inverse scattering problem while accounting for multiple light scattering. We proposed a discrete image-processing theory to compute the error backpropagation of vectorially diffracting light. Finally, our theory was experimentally demonstrated using both synthetic and biologically birefringent samples.

Carryover Effects of Pain Neuroscience Education on Patients with Chronic Lower Back Pain: A Systematic Review and Meta-Analysis.

Background and Objectives: Because most individuals with chronic back pain (CLBP) have no specific cause, it is usually described as central sensitization. Pain neuroscience education (PNE) in top-down pain control may be effective against carryover effects; however, this remains unclear. In this study, the carryover effect was qualitatively and quantitatively synthesized and analyzed. Materials and Methods: Randomized controlled trials (RCTs) on PNE in individuals with CLBP were conducted using international databases until January 2023. Using RevMan5.4 provided by Cochrane, qualitative and quantitative analyses were performed with a risk of bias and meta-analysis, respectively. Results: Nine RCTs involving 1038 individuals with CLBP were included in the analysis. Four main results were identified: First, PNE had a short-term carryover effect on pain intensity (SMD = -1.55, 95% confidence interval [CI] = -2.59 to -0.50); second, PNE had a short-term carryover effect on pain catastrophizing (SMD = -2.47, 95% CI = -3.44 to -1.50); third, PNE had short- and long-term carryover effects on kinesiophobia (SMD = -3.51, 95% CI = -4.83 to -2.19); fourth, the appropriate therapeutic intensity of PNE for the pain intensity of individuals (SMD = -0.83, 95% CI = -1.60 to -0.07). Conclusions: PNE has a short-term carryover effect on pain intensity and pain cognition in individuals with CLBP and a long-term carryover effect on kinesiophobia.

Robot-assisted radial forearm free flap harvesting: a propensity score-matched case-control study.

Although some surgeons prefer anterolateral thigh and latissimus dorsi flap for soft tissue reconstruction in the head and neck area because it minimizes donor site complications, the radial forearm flap remains the workhorse for soft tissue reconstruction due to its reliability. To reduce donor site morbidity, the authors developed a novel technique for radial forearm flap harvesting using a robotic device. 42 radial forearm free flap reconstruction cases were studied, consisting of 31 conventional and 11 robot-assisted cases. 1:1 propensity score matching was done according to age, sex, previous and postoperative radiation therapy history and method used for vein anastomosis. There was no significant difference in flap outcome, which was 100% vitality in the robot-assisted group and 90.9% vitality in the conventional group. The robot-assisted group showed significantly longer mean harvesting time than did the conventional group, being 107.2 min and 67.0 min, respectively. Robot-assisted radial forearm flap harvesting can reduce donor site complications by minimizing incision. When more surgical experience is gained under appropriate case selection, we expect our robot-assisted method will yield a harvesting time similar to that of the conventional method and thus become more reliable and feasible.

Regularization of dielectric tensor tomography.

Dielectric tensor tomography reconstructs the three-dimensional dielectric tensors of microscopic objects and provides information about the crystalline structure orientations and principal refractive indices. Because dielectric tensor tomography is based on transmission measurement, it suffers from the missing cone problem, which causes poor axial resolution, underestimation of the refractive index, and halo artifacts. In this study, we study the application of total variation and positive semi-definiteness regularization to three-dimensional tensor distributions. In particular, we demonstrate the reduction of artifacts when applied to dielectric tensor tomography.

Micro-replication platform for studying the structural effect of seed surfaces on wetting properties.

Biological surfaces in plants are critical for controlling essential functions such as wettability, adhesion, and light management, which are linked to their adaptation, survival, and reproduction. Biomimetically patterned surfaces replicating the microstructures of plant surfaces have become an emerging tool for understanding plant-environment interactions. In this study, we developed a two-step micro-replication platform to mimic the microstructure of seed surfaces and demonstrated that this initial platform can be used to study seed surface-environment interactions. The two-step process involved the extraction of a simplified seed surface model from real seeds and micro-replication of the simplified seed surface model using nanoimprint lithography. Using Allium seeds collected from Mongolia and Central Asia as the model system, we studied the wettability of biological and synthetic seed surfaces. We could independently control the material properties of a synthetic seed surface while maintaining the microstructures and, thereby, provide clear evidence that Allium seed surfaces were highly wettable owing to the high surface energy in the epidermal material rather than a microstructural effect. We expect that this platform can facilitate study of the independent effect of microstructure on the interaction of seed surfaces with their surroundings and contribute to research on the evolution of plant-environment interactions.

Tomographic measurement of dielectric tensors at optical frequency.

The dielectric tensor is a physical descriptor of fundamental light-matter interactions, characterizing anisotropic materials with principal refractive indices and optic axes. Despite its importance in scientific and industrial applications ranging from material science to soft matter physics, the direct measurement of the three-dimensional dielectric tensor has been limited by the vectorial and inhomogeneous nature of light scattering from anisotropic materials. Here, we present a dielectric tensor tomographic approach to directly measure dielectric tensors of anisotropic structures including the spatial variations of principal refractive indices and directors. The anisotropic structure is illuminated with a polarized plane wave with various angles and polarization states. Then, the scattered fields are holographically measured and converted into vectorial diffracted field components. Finally, by inversely solving a vectorial wave equation, the three-dimensional dielectric tensor is reconstructed. Using this approach, we demonstrate quantitative tomographic measurements of various nematic liquid-crystal structures and their fast three-dimensional non-equilibrium dynamics.

Noma disease (cancrum oris, orofacial gangrene) in an acute myeloid leukemia patient: a case report.

BACKGROUND: Noma is a rare disease that occurs mainly in malnourished patients in developing countries. Noma starts as facial swelling and gingival necrosis that eventually necrotizes underlying tissues including the jaw bone, leaving severe disfigurement. It is reported extremely rarely in patients with severe immunosuppression or blood dyscrasia. CASE PRESENTATION: The gingivitis that occurred in a 12-year-old Asian female patient with acute myeloid leukemia was getting increasingly worse. Although the proper treatment was done, the patient's condition did not improve, and eventually, a large full-thickness defect was left in the maxillofacial part. CONCLUSIONS: Early diagnosis and management is the only way to prevent the progression, which leads to facial disfigurement. We present a case of noma in a pediatric acute myeloid leukemia patient, in which oral function was restored through surgical intervention.

Spatially multiplexed dielectric tensor tomography.

Dielectric tensor tomography (DTT) enables the reconstruction of three-dimensional (3D) dielectric tensors, which provides a physical measure of 3D optical anisotropy. Herein, we present a cost-effective and robust method of DTT using spatial multiplexing. Exploiting two orthogonally polarized reference beams with different angles in an off-axis interferometer, two polarization-sensitive interferograms were multiplexed and recorded using a single camera. Then, the two interferograms were demultiplexed in the Fourier domain. By measuring the polarization-sensitive fields for various illumination angles, 3D dielectric tensor tomograms were reconstructed. The proposed method was experimentally demonstrated by reconstructing the 3D dielectric tensors of various liquid-crystal (LC) particles with radial and bipolar orientational configurations.

Detection of intracellular monosodium urate crystals in gout synovial fluid using optical diffraction tomography.

Optical diffraction tomography (ODT) enables imaging of unlabeled intracellular components by measuring the three-dimensional (3D) refractive index (RI). We aimed to detect intracellular monosodium urate (MSU) crystals in synovial leukocytes derived from gout patients using ODT. The 3D RI values of the synthetic MSU crystals, measured by ODT, ranged between 1.383 and 1.440. After adding synthetic MSU crystals to a macrophage, RI tomograms were reconstructed using ODT, and the reconstructed RI tomograms discerned intracellular and extracellular MSU crystals. We observed unlabeled synthetic MSU crystal entry into the cytoplasm of a macrophage through time-lapse imaging. Furthermore, using gout patient-derived synovial leukocytes, we successfully obtained RI tomogram images of intracellular MSU crystals. The 3D RI identification of MSU crystals was verified with birefringence through polarization-sensitive ODT measurements. Together, our results provide evidence that this novel ODT can identify birefringent MSU crystals in synovial leukocytes of patients with gout.

Three-dimensional evaluation of the correlation between lip canting and craniofacial planes.

OBJECTIVE: This study aimed to analyze the correlation of horizontal and sagittal planes used in two-dimensional diagnosis with lip canting by using threedimensional (3D) analysis. METHODS: Fifty-two patients (25 men, 27 women; average age: 24 years) undergoing treatment for dentofacial deformity were enrolled. Computed tomography images were acquired, and digital imaging and communication in medicine files were reconstructed into a 3D virtual model wherein horizontal and sagittal craniofacial planes were measured. Subsequently, the correlations of lip canting with these horizontal and sagittal planes were investigated. RESULTS: The mandibular symmetry plane, the occlusal plane, Camper's plane, the mandibular plane, Broadbent's plane, and the nasal axis plane were correlated with the amount of lip canting (Pearson's correlation coefficients: 0.761, 0.648, 0.556, 0.526, 0.438, and 0.406, respectively). Planes associated with the lower part of the face showed the strongest correlations; the strength of the correlations decreased in the midfacial and cranial regions. None of the planes showed statistically significant differences between patients with clinical lip canting (> 3°) and those without prominent lip canting. CONCLUSIONS: The findings of this study suggest that lip canting is strongly correlated with the mandibular symmetry plane, which includes menton deviation. This finding may have clinical implications with regard to the treatment of patients requiring correction of lip canting. Further studies are necessary for evaluating changes in lip canting after orthognathic surgery.

Effects of air pollution on moderate and severe asthma exacerbations.

Background: Few studies have evaluated the impact of air pollution levels on the severity of exacerbations. Thus, we compared the relative risks posed by air pollutant levels on moderate and severe exacerbations.Methods: Exacerbation episodes of 618 from 143 adult asthmatics were retrospectively collected between 2005 and 2015 in a tertiary hospital of Korea. Air pollution GPS data for the location closest to each patient's home were obtained from the national ambient monitoring station. The relative impacts of air pollutants on asthma exacerbations were evaluated via a time-trend controlled symmetrical, bidirectional, case-crossover design using conditional logistic regression models on the day of the exacerbation (T-0) and up to 3 days before the exacerbation (T-1-T-3).Results: Overall asthma exacerbation were associated with O3 levels in summer and winter (OR: 1.012[1.003-1.02] and 1.009[1.003-1.016]), SO2 levels in spring and summer (OR: 1.009[1-1.018] and 1.02[1.006-1.035]) and NO2 levels in winter (OR: 1.007[1.003-1.011]). Analyses of the temporal relationship between O3 concentrations and exacerbations demonstrated that 63.2% of episodes in the summer occurred when the O3 concentrations on T-1 were significantly higher than those on control days, while 51% of exacerbation episodes in the winter occurred. Severe and moderate exacerbations were similarly associated with O3 levels in winter (OR: 1.012 [1.003-1.02] vs. 1.01 [0.999-1.021], p > 0.05) and in summer (OR: 1.006 [1.002-1.009] vs. 1.009 [1.003-1.016], p > 0.05).Conclusions: Asthma exacerbations may be associated with the seasonal elevation of O3, SO2 and NO2 levels in summer and winter with the similar relative risk between moderate and severe exacerbations.

Global DNA Methylation Pattern of Fibroblasts in Idiopathic Pulmonary Fibrosis.

Our previous transcriptome study of cultured fibroblasts identified 178 genes that were differentially expressed by 8 idiopathic pulmonary fibrosis (IPF) fibroblasts compared with 4 controls. Here, we performed genome-wide DNA methylation analysis to evaluate the relationship of CpG methylation to differential gene expression. Among 485,577 loci, 5850 loci on 2282 genes showed significant differences between the 2 groups (delta-beta >10.21 and p-value <0.05). Among these, beta values of 80 CpGs (30 hypermethylated and 50 hypomethylated) were significantly correlated with mRNA expression of 34 genes (19.1%) of the 178 differentially expressed genes between the 2 groups (13 downregulated and 21 upregulated). Gene ontology enrichment of these genes included cell adhesion, molecule binding, chemical homeostasis, surfactant homeostasis, and receptor binding. One-third of them are involved in the known process of fibrosis; the others are novel genes with respect to pulmonary fibrosis. We identified relationships between the altered DNA methylation levels and about one-fifth of the corresponding changes in gene expression by lung tissue fibroblasts. Findings from this study provide new information on novel genes responsible for the pathogenesis of IPF under the control of CpG methylation changes in IPF lungs.

Low-coherent optical diffraction tomography by angle-scanning illumination.

Temporally low-coherent optical diffraction tomography (ODT) is proposed and demonstrated based on angle-scanning Mach-Zehnder interferometry. Using a digital micromirror device based on diffractive tilting, the full-field interference of incoherent light is successfully maintained during every angle-scanning sequences. Further, current ODT reconstruction principles for temporally incoherent illuminations are thoroughly reviewed and developed. Several limitations of incoherent illumination are also discussed, such as the nondispersive assumption, optical sectioning capacity and illumination angle limitation. Using the proposed setup and reconstruction algorithms, low-coherent ODT imaging of plastic microspheres, human red blood cells and rat pheochromocytoma cells is experimentally demonstrated.

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.

Reference-free polarization-sensitive quantitative phase imaging using single-point optical phase conjugation.

We propose and experimentally demonstrate a method of polarization-sensitive quantitative phase imaging using two photodetectors and a digital micromirror device. Instead of recording wide-field interference patterns, finding the modulation patterns maximizing focused intensities in terms of the polarization states enables polarization-dependent quantitative phase imaging without the need for a reference beam and an image sensor. The feasibility of the present method is experimentally validated by reconstructing Jones matrices of several samples including a polystyrene microsphere, a maize starch granule, and a mouse retinal nerve fiber layer. Since the present method is simple and sufficiently general, we expect that it may offer solutions for quantitative phase imaging of birefringent materials.

Generalized quantification of three-dimensional resolution in optical diffraction tomography using the projection of maximal spatial bandwidths.

Optical diffraction tomography (ODT) is a three-dimensional (3D) quantitative phase imaging technique, which enables the reconstruction of the 3D refractive index (RI) distribution of a transparent sample. Due to its fast, non-invasive, and quantitative imaging capability, ODT has emerged as a powerful tool for various applications. However, the spatial resolution of ODT has only been quantified along the lateral and axial directions for limited conditions; it has not been investigated for arbitrary-oblique directions. In this paper, we systematically quantify the 3D spatial resolution of ODT by exploiting the spatial bandwidth of the reconstructed scattering potential. The 3D spatial resolution is calculated for various types of systems, including the illumination-scanning, sample-rotation, and hybrid scanning-rotation methods. In particular, using the calculated 3D spatial resolution, we provide the spatial resolution as well as the arbitrary sliced angle. Furthermore, to validate the present method, the point spread function of an ODT system is experimentally obtained using the deconvolution of a 3D RI distribution of a microsphere and is compared with the calculated resolution.

Enhancement of optical resolution in three-dimensional refractive-index tomograms of biological samples by employing micromirror-embedded coverslips.

Optical diffraction tomography (ODT) enables the reconstruction of the three-dimensional (3D) refractive-index (RI) distribution of a biological cell, which provides invaluable information for cellular and subcellular structures in a non-invasive manner. However, ODT suffers from an inferior axial resolution, due to the limited accessible angles imposed by the numerical aperture of the objective lens. In this study, we propose and experimentally demonstrate an approach to enhance the 3D reconstruction performance in ODT. By employing trapezoidal micromirrors, side scattered signals from the sample are measured for various side plane-wave-illumination angles. By combining the side scattered fields with the forward scattered fields, the axial resolution and 3D image quality of ODT are improved, without changing optical instruments. The feasibility and applicability of the proposed method are demonstrated by reconstructing the 3D RI distribution of a red blood cell and HeLa cells in hydrogel. We also present systematic analyses of the improved 3D imaging performance using numerical simulations and experimental measurements for the 3D transfer function, a point object, and a microsphere. The analyses demonstrate an improved axial resolution of 0.31 µm, 4.8 times smaller than that of the conventional method. The proposed method enables the non-invasive and accurate 3D imaging of 3D cultured cells, which is crucial for cell biology studies.

Combining Three-Dimensional Quantitative Phase Imaging and Fluorescence Microscopy for the Study of Cell Pathophysiology.

Quantitative phase imaging (QPI) has emerged as one of the powerful imaging tools for the study of live cells in a non-invasive manner. In particular, multimodal approaches combining QPI and fluorescence microscopic techniques have been recently developed for superior spatiotemporal resolution as well as high molecular specificity. In this review, we briefly summarize recent advances in three-dimensional QPI combined with fluorescence techniques for the correlative study of cell pathophysiology. Through this review, biologists and clinicians can be provided with insights on this rapidly growing field of research and may find broader applications to investigate unrevealed nature in cell physiology and related diseases.

Super-resolution three-dimensional fluorescence and optical diffraction tomography of live cells using structured illumination generated by a digital micromirror device.

We present a multimodal approach for measuring the three-dimensional (3D) refractive index (RI) and fluorescence distributions of live cells by combining optical diffraction tomography (ODT) and 3D structured illumination microscopy (SIM). A digital micromirror device is utilized to generate structured illumination patterns for both ODT and SIM, which enables fast and stable measurements. To verify its feasibility and applicability, the proposed method is used to measure the 3D RI distribution and 3D fluorescence image of various samples, including a cluster of fluorescent beads, and the time-lapse 3D RI dynamics of fluorescent beads inside a HeLa cell, from which the trajectory of the beads in the HeLa cell is analyzed using spatiotemporal correlations.

Label-free non-invasive quantitative measurement of lipid contents in individual microalgal cells using refractive index tomography.

Microalgae are promising candidates for biofuel production due to their high lipid content. To facilitate utilization of the microalgae for biofuel, rapid quantification of the lipid contents in microalgae is necessary. However, conventional methods based on the chemical extraction of lipids require a time-consuming destructive extraction process. Here, we demonstrate label-free, non-invasive, rapid quantification of the lipid contents in individual micro-algal cells measuring the three-dimensional refractive index tomograms. We measure three-dimensional refractive index distributions within Nannochloropsis oculata cells and find that lipid droplets are identifiable in tomograms by their high refractive index. In addition, we alter N. oculata under nitrogen deficiency by measuring the volume, lipid weight, and dry cell weight of individual cells. Characterization of individual cells allows correlative analysis between the lipid content and size of individual cells.