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Multiphoton microscopy is the current method of choice for in vivo deep-tissue imaging. The long laser wavelength suffers less scattering, and the 3D-confined excitation permits the use of scattered signal light. However, the imaging depth is still limited because of the complex refractive index distribution of biological tissue, which scrambles the incident light and destroys the optical focus needed for high resolution imaging. Here, we demonstrate a wavefront-shaping scheme that allows clear imaging through extremely turbid biological tissue, such as the skull, over an extended corrected field of view (FOV). The complex wavefront correction is obtained and directly conjugated to the turbid layer in a noninvasive manner. Using this technique, we demonstrate in vivo submicron-resolution imaging of neural dendrites and microglia dynamics through the intact skulls of adult mice. This is the first observation, to our knowledge, of dynamic morphological changes of microglia through the intact skull, allowing truly noninvasive studies of microglial immune activities free from external perturbations. Significance Multiphoton microscopy has been the gold standard for in vivo deep-tissue imaging. The long laser wavelength suffers less scattering, and the 3D-confined excitation permits the use of scattered signal light, which greatly improves the imaging depth. However, the direct application of this method to highly turbid media has been limited. Here, we present a microscope system demonstrating high resolution in vivo imaging inside highly turbid tissue. We use advanced wavefront correction with an adaptive correction plane-positioning system to compensate high-order aberrations over an extended corrected field of view. Using this technique, we demonstrate submicron-resolution imaging of neural dendrites and microglia dynamics through the intact skulls of adult mice.

Decoupling dynamic touch signals in the optical tactile sensors is highly desired for behavioral tactile applications yet challenging because typical optical sensors mostly measure only static normal force and use imprecise multi-image averaging for dynamic force sensing. Here, we report a highly sensitive upconversion nanocrystals-based behavioral biometric optical tactile sensor that instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. By mimicking the sensory architecture of human skin, the unique luminescence signal obtained is axisymmetric for static normal forces and non-axisymmetric for dynamic shear forces. Our sensor demonstrates high spatio-temporal screening of small objects and recognizes fingerprints for authentication with high spatial-temporal resolution. Using a dynamic force discrimination machine learning framework, we realized a Braille-to-Speech translation system and a next-generation dynamic biometric recognition system for handwriting. A sensitive upconversion nanocrystal-based biometric optical tactile sensor instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 μs) were significantly increased compared to the short pulse duration-treated groups (100 μs) (all p  < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

Prophylactic embolization is usually performed using gelatin sponge particles, which are absorbed within several weeks, for managing angiographically negative gastrointestinal bleeding. This study aimed to evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with quick-soluble gelatin sponge particles (QS-GSP) that dissolve in less than 4 h for treating angiographically negative gastrointestinal bleeding. We included ten patients (M:F = 7:3; mean age, 64.3 years) who underwent prophylactic TAE with QS-GSP for angiographically negative acute gastrointestinal bleeding between 2021 and 2023. The technical success rate of TAE, clinical outcomes focusing on rebleeding, and procedure-related complications were evaluated. The embolized arteries were the gastroduodenal (n = 3), jejunal (n = 4), and ileal (n = 3) arteries. QS-GSP (150–350 µm or 350–560 µm) were used alone (n = 8) or in combination with a coil (n = 1). A 100% technical success rate was accomplished. In 1 patient (10%), rebleeding occurred 2 days after prophylactic TAE of the gastroduodenal artery, and this was managed by repeat TAE. There were no procedure-related complications. The use of QS-GSP for prophylactic TAE appears to be safe and effective for controlling bleeding among patients with angiographically negative gastrointestinal bleeding. There were no cases of related ischemic complications of the embolized bowels likely attributable to recanalization of the affected arteries following biodegradation of QS-GSP.

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies. Periodic patterns with varying cross-linking densities are realized in conjugated polydiacetylene films, creating multiple holographic images—all dynamically responsive to exposure to various solvents—simultaneously in the same polymeric structures.

Although balloon dilation has shown promising results in the treatment of dilatory Eustachian tube (ET) dysfunction, the histological effects of ET balloon dilation (ETBD) is unknown because histological examination of the whole human cartilaginous ET is impossible. Animal studies are needed to elucidate the effect of ETBD so we evaluated the histological changes after ETBD in a rat model. The left ET of 20 Wistar rats was dilated with a balloon catheter and the right ET was used as a control. Five rats were sacrificed immediately after ETBD, at 1, 4 and 12 weeks after the procedure for histological examination. The epithelial cells, presence of epithelial hyperplasia, and the proportion of the goblet cells in the epithelium; the vascular structures and dimensions of the submucosa; and presence of cartilage fracture and the area of the ET lumen were evaluated and compared between the groups. Desquamation of nearly all epithelial cells and the fracture of tubal cartilages were observed immediately after ETBD. At 1-week post-ETBD, the ciliated epithelial cells started to recover with epithelial hyperplasia. The goblet cells recovered by 4 weeks post-ETBD and epithelial hyperplasia decreased but was still present at 12 weeks post-ETBD. The depth of the submucosa increased and neovascularization in this region was observed at 1-week post-ETBD and persisted up to 12 weeks post-ETBD. The lumen of the cartilaginous ET increased immediately after ETBD but decreased at 1-week post-ETBD. The cartilaginous ET lumen recovered to the normal value at 4 weeks post-ETBD. This study is the first to describe the serial histological changes to the cartilaginous ET after ETBD and helps our understanding of the histological changes that occur after an ETBD intervention for intractable ET dysfunction.

Various preclinical studies with developed Eustachian tube (ET) stents are in progress but have not yet been clinically applied. ET stent is limited by stent-induced tissue hyperplasia in preclinical studies. The effectiveness of sirolimus-eluting cobalt–chrome alloy stent (SES) in suppressing stent-induced tissue hyperplasia after stent placement in the porcine ET model was investigated. Six pigs were divided into two groups (i.e., the control and the SES groups) with three pigs for each group. The control group received an uncoated cobalt–chrome alloy stent ( n  = 6), and the SES group received a sirolimus-eluting cobalt–chrome alloy stent ( n  = 6). All groups were sacrificed 4 weeks after stent placement. Stent placement was successful in all ETs without procedure-related complications. None of the stents was able to keep its round shape as original, and mucus accumulation was observed inside and around the stent in both groups. On histologic analysis, the tissue hyperplasia area and the thickness of submucosal fibrosis were significantly lower in the SES group than in the control group. SES seems to be effective in suppressing stent-induced tissue hyperplasia in porcine ET. However, further investigation was required to verify the optimal stent materials and antiproliferative drugs.

Absorbable magnesium (Mg) stents have an attractive biocompatibility and rapid degradation rate, but their degradable behavior and efficacy in the Eustachian tube (ET) have not yet been investigated. In this study, the degradable behavior of the Mg stent in artificial nasal mucus was evaluated. The Mg stents in the porcine ET model were also investigated to evaluate their safety and efficacy. Four Mg stents were placed into the four ETs of two pigs. The mass loss rate of the Mg stents gradually decreased over time. The decrease rates were 30.96% at one week, 49.00% at two weeks, and 71.80% at four weeks. On the basis of histological findings, the thickness of submucosal tissue hyperplasia and the degree of inflammatory cell infiltration significantly decreased at four weeks compared with two weeks. Biodegradation of the Mg stent occurred before tissue proliferative reactions, and the ET patency was successfully maintained without stent-induced tissue hyperplasia at four weeks. The Mg stent that biodegrades rapidly seems to be effective and safe in porcine ET. Further investigation is required to verify the optimal stent shape and indwell period in the ET.

Minimally invasive therapies using stent technology are currently limited by stent-induced granulation tissue formation adjacent to the stent. The effectiveness of photothermal therapy (PTT) using a gold nanoparticle (AuNP)-coated stent for treating stent-induced granulation tissue formation in the rat esophagus was investigated. All experiments were approved by the animal research committee of our institution. An AuNP-coated, self-expandable metallic stent (SEMS) was produced to conduct PTT under near-infrared laser irradiation. Forty rats were randomly divided into four groups (10 rats each). The animals in group A (non-coated SEMS) and group B (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) were sacrificed 4 weeks after stent placement. The rats in group C (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) and group D (AuNP-coated SEMS with local heating at 65 °C at 4 and 8 weeks) were sacrificed 8 weeks after stent placement. The effectiveness of local heating was assessed by histopathology. All procedures were successful in all of the animals. Seven rats were excluded because of stent migration (n = 2) and death (n = 5). Granulation tissue formation-related variables were significantly higher in group A than in groups B–D (all p  < 0.05). Heat-shock protein 70 (HSP70) and TUNEL expression were significantly lower in group A than in groups B–D (all p  < 0.05). Granulation tissue formation-related variables were significantly higher in group C than in groups B and D (all p  < 0.05). PTT using AuNP-coated SEMS successfully treated granulation tissue formation after stent placement in the rat esophagus.

Obtaining depth-selective images requires gating procedures such as spatial, nonlinear, or coherence gating to differentiate light originating from different depths of the volume of interest. Nonlinear gating requires pulsed excitation sources and excitation probes, limiting easy usage. Coherence gating also requires broadband sources and interferometry requiring specialized stable setups. Spatial gating can be used both for fluorescence and reflection geometry and various light sources and thus has the least requirements on hardware, but still requires the use of a pinhole which makes it difficult to use for photography or widefield imaging schemes. Here, we demonstrate that we can utilize a single digital micromirror device (DMD) to simultaneously function as a dynamic illumination modulator and automatically synchronized dynamic pinhole array to obtain depth-sectioned widefield images. Utilizing the multiplexed measurement advantage of single-pixel imaging, we show that the depth and ballistic light gating of the confocal single pixel imaging scheme can be utilized to obtain images through glare and multiple scattering where conventional widefield imaging fails to recover clear images due to saturation or random scattered noise.