Hydrogels are widely used as scaffold materials for constructingin vitrothree-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enablesin situcell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform,in situcell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications.
Hydrogels , Liver , Humans , Hydrogels/chemistry , Collagen , Hepatocytes , Hep G2 Cells
Spiral-phase-contrast imaging, which utilizes a spiral phase optical element, has proven to be effective in enhancing various aspects of imaging, such as edge contrast and shadow imaging. Typically, the implementation of spiral-phase-contrast imaging requires the formation of a Fourier plane through a 4f optical configuration in addition to an existing optical microscope. In this study, we present what we believe to be a novel single spiral-phase-objective, integrating a spiral phase plate, which can be easily and simply applied to a standard microscope, such as a conventional objective. Using a new hybrid design approach that combines ray-tracing and field-tracing simulations, we theoretically realized a well-defined and high-quality vortex beam through the spiral-phase-objective. The spiral-phase-objective was designed to have conditions that are practically manufacturable while providing predictable performance. To evaluate its capabilities, we utilized the designed spiral-phase-objective to investigate isotropic spiral phase contrast and anisotropic shadow imaging through field-tracing simulations, and explored the variation of edge contrast caused by changes in the thickness of the imaging object.
Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique. Here, we present a method to integrate optical coherence tomography (OCT) and SECM for complementary imaging by adding orthogonal scanning to the SECM configuration. The co-registration of SECM and OCT is automatic, as all system components are shared in the same order, eliminating the need for additional optical alignment. The proposed multimode imaging system is compact and cost-effective while providing the benefits of imaging aiming and guidance. Furthermore, speckle noise can be suppressed by averaging the speckles generated by shifting the spectral-encoded field in the direction of dispersion. Using a near infrared (NIR) card and a biological sample, we demonstrated the capability of the proposed system by showing SECM imaging at depths of interest guided by the OCT in real time and speckle noise reduction. Interfaced multimodal imaging of SECM and OCT was implemented at a speed of approximately 7 frames/s using fast-switching technology and GPU processing.
Biochip-based research is currently evolving into a three-dimensional and large-scale basis similar to the in vivo microenvironment. For the long-term live and high-resolution imaging in these specimens, nonlinear microscopy capable of label-free and multiscale imaging is becoming increasingly important. Combination with non-destructive contrast imaging will be useful for effectively locating regions of interest (ROI) in large specimens and consequently minimizing photodamage. In this study, a label-free photothermal optical coherence microscopy (OCM) serves as a new approach to locate the desired ROI within biological samples which are under investigation by multiphoton microscopy (MPM). The weak photothermal perturbation in sample by the MPM laser with reduced power was detected at the endogenous photothermal particles within the ROI using the highly sensitive phase-differentiated photothermal (PD-PT) OCM. By monitoring the temporal change of the photothermal response signal of the PD-PT OCM, the hotspot generated within the sample focused by the MPM laser was located on the ROI. Combined with automated sample movement in the x-y axis, the focal plane of MPM could be effectively navigated to the desired portion of a volumetric sample for high-resolution targeted MPM imaging. We demonstrated the feasibility of the proposed method in second harmonic generation microscopy using two phantom samples and a biological sample, a fixed insect on microscope slide, with dimensions of 4 mm wide, 4 mm long, and 1 mm thick.
Microscopy , Movement , Phantoms, Imaging
Wavelength-tunable spiral-phase-contrast (SPC) imaging was experimentally accomplished in the visible wavelengths spanning a broad bandwidth of â¼200 nm based on a single off-axis spiral phase mirror (OSPM). By the rotation of an OSPM, which was designed with an integer orbital angular momentum (OAM) of l = 1 at a wavelength of 561 nm and incidence angle of 45°, high-quality SPC imaging was obtained at different wavelengths. For the comparison with wavelength-tunable SPC imaging using an OSPM, SPC imaging using a spiral phase plate (manufactured to generate an OAM of l = 1 at 561 nm) was performed at three wavelengths (473, 561, and 660 nm), resulting in clear differences. Theoretically, based on field tracing simulations, high-quality wavelength-tunable SPC imaging could be demonstrated in a very broad bandwidth of â¼400 nm, which is beyond the bandwidth of â¼200 nm obtained experimentally. This technique contribute to developing high-performance wavelength-tunable SPC imaging by simply integrating an OSPM into the current optical imaging technologies.
This publisher's note contains corrections to Opt. Lett.46, 4216 (2021)OPLEDP0146-959210.1364/OL.432413.
Wavelength-tunable optical vortices with a topological charge equal to l=1 of orbital angular momentum (OAM) were experimentally realized using a single off-axis spiral phase mirror (OSPM) with lasers of various visible-light wavelengths. Using an OSPM designed for 561 nm and an incidence angle of 45°, circular doughnut-shaped l=1 optical vortices were obtained at 561, 473, and 660 nm by rotating the OSPM to modify the laser incidence angle. Wavelength-tunable l=1 optical vortices were obtained at the respective incidence angles of 45°, 53.4°, and 33.7°, because the effective geometrical thickness of the OSPM, which determines the order of OAM, was identical at each wavelength. This flexible OSPM which operates over a wide wavelength range will provide continuously wavelength-tunable optical vortices for applications in the fields of advanced optics and photonics in which optical vortices with wide wavelength tunability are in demand.
Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.
Breast Neoplasms , Metal Nanoparticles , Nanotubes , Breast Neoplasms/therapy , Cell Line, Tumor , Female , Gold , Humans , Metal Nanoparticles/therapeutic use , Phototherapy
Background and Objectives: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. Materials and Methods: Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. Results: Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. Conclusions: CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis.
Cognitive Behavioral Therapy , Migraine Disorders , Disability Evaluation , Headache/therapy , Humans , Migraine Disorders/therapy , Pain Measurement
In this study, a portable and large-area blackbody system was developed following a series of processes including design, computational analysis, fabrication, and experimental analysis and evaluation. The blackbody system was designed to be lightweight (5 kg), and its temperature could exceed the ambient temperature by up to 15 °C under operation. A carbon-fiber-based heat source was used to achieve a uniform temperature distribution. A heat shield fabricated from an insulation material was embedded at the opposite side of the heating element to minimize heat loss. A prototype of the blackbody system was fabricated based on the design and transient coupled electro-thermal simulation results. The operation performance of this system, such as the thermal response, signal transfer function, and noise equivalent temperature difference, was evaluated by employing an infrared imaging system. In addition, emissivity was measured during operation. The results of this study show that the developed portable and large-area blackbody system can be expected to serve as a reliable reference source for the calibration of aerial infrared images for the application of aerial infrared techniques to remote sensing.
We report a new, to the best of our knowledge, approach to correct image blurring due to the axial bulk motion of a sample in wavelength-sweeping Fourier domain parallel optical coherence tomography (OCT). This approach can estimate phase errors changing rapidly in time through direct measurements of the apparent axial shift during the sampling interval using common phase changes in parallel detection without additional hardware. To demonstrate the performance of the proposed algorithm, a single reflection and scattering sample were imaged with wavelength-sweeping parallel OCT implemented by scanning a spectrally dispersed line-field along the line direction. In addition, we quantitatively demonstrated that even a small axial movement of the sample could cause serious image blur at a high nonlinear degree of movement.
The periodic structure on the optical surface affects the beam shape and its propagation. As the size of the optical elements becomes larger and its shape becomes complicated, the quantitative analysis of the effect of the periodic structure on the optical surface becomes indispensable given that it is very difficult to completely eliminate the microscopic periodic structures. Herein, we have experimentally investigated Bragg scattering from an optical surface with extremely small aspect ratios (~10-5) and groove densities (0.5 lines/mm). We observed the period of the constructive interference formed due to the propagation of the 0th, 1st, and -1st beam modes caused by Bragg scattering. When the periodic structure has a modulation depth of ± 50 nm, the intensity increase of constructive interference between the beam modes formed by Bragg scattering was > 10 times greater than the intensity of a flat surface at the propagation distance at which constructive interference was most pronounced. This study is envisaged to open new avenues for the quantification of the effect of periodic structures based on the observation of the interference on the beam profile formed by Bragg scattering during the beam propagation.
Micro-electronic devices are increasingly incorporating miniature multi-layered integrated architectures. However, the localization of faults in three-dimensional structure remains challenging. This study involved the experimental and numerical estimation of the depth of a thermally active heating source buried in multi-layered silicon wafer architecture by using both phase information from an infrared microscopy and finite element simulation. Infrared images were acquired and real-time processed by a lock-in method. It is well known that the lock-in method can increasingly improve detection performance by enhancing the spatial and thermal resolution of measurements. Operational principle of the lock-in method is discussed, and it is represented that phase shift of the thermal emission from a silicon wafer stacked heat source chip (SSHSC) specimen can provide good metrics for the depth of the heat source buried in SSHSCs. Depth was also estimated by analyzing the transient thermal responses using the coupled electro-thermal simulations. Furthermore, the effects of the volumetric heat source configuration mimicking the 3D through silicon via integration package were investigated. Both the infrared microscopic imaging with the lock-in method and FE simulation were potentially useful for 3D isolation of exothermic faults and their depth estimation for multi-layered structures, especially in packaged semiconductors.
PURPOSE: Although trans-portal and outside-in techniques are commonly used for anatomical ACL reconstruction, there is very little information on variability in tunnel placement between two techniques. METHODS: A total of 103 patients who received ACL reconstruction using trans-portal (50 patients) and outside-in techniques (53 patients) were included in the study. The ACL tunnel location, length and graft-femoral tunnel angle were analyzed using the 3D CT knee models, and we compared the location and length of the femoral and tibial tunnels, and graft bending angle between the two techniques. The variability in each technique regarding the tunnel location, length and graft tunnel angle using the range values was also compared. RESULTS: There were no differences in the average of femoral tunnel depth and height between the two groups. The ranges of femoral tunnel depth and height showed no difference between two groups (36 and 41 % in trans-portal technique vs. 32 and 41 % in outside-in technique). The average value and ranges of tibial tunnel location also showed similar results in two groups. The outside-in technique showed longer femoral tunnel than the trans-portal technique (34.0 vs. 36.8 mm, p = 0.001). The range of femoral tunnel was also wider in trans-portal technique than in outside-in technique. Although the outside-in technique showed significant acute graft bending angle than trans-portal technique in average values, the trans-portal technique showed wider ranges in graft bending angle than outside-in technique [ranges 73° (SD 13.6) vs. 53° (SD 10.7), respectively]. CONCLUSIONS: Although both trans-portal and outside-in techniques in ACL reconstruction can provide relatively consistent in femoral and tibial tunnel locations, trans-portal technique showed high variability in femoral tunnel length and graft bending angles than outside-in technique. Therefore, the outside-in technique in ACL reconstruction is considered as the effective method for surgeons to make more consistent femoral tunnel. LEVEL OF EVIDENCE: III.
Anterior Cruciate Ligament Reconstruction/methods , Femur/surgery , Tibia/surgery , Anterior Cruciate Ligament/surgery , Humans
The anatomic transtibial (TT) technique is proposed as a new approach for single-bundle anterior cruciate ligament (ACL) reconstruction. Geometric models of the anatomic TT and anteromedial (AM) portal techniques were fabricated with a reconstructed knee joint model and virtual surgical operations. Grafts of 7 mm diameter were modeled and inserted into tunnels drilled in each model. In the models, the shape of the graft between the femur and the tibia, the lengths of the bone tunnels, and the femoral graft bending angles were evaluated. To evaluate the biomechanical effects of both techniques on the grafts, the contact pressures and maximum principal stresses in the grafts were calculated using the finite element method. The anatomic TT technique placed the femoral tunnel to the anatomic position of the native ACL femoral attachment site. In addition, it decreased the peak contact pressure and the maximum principal stress at the full extension position of the graft compared with the AM portal technique. The anatomic TT technique may be regarded as a superior surgical technique compared with the conventional TT and AM portal techniques. Because of the easy surgical operation involved, the technique decreases the operation time for ACL reconstruction and it provides a deformation behavior of grafts similar to that in the native ACL in a knee joint. With its few side effects, the anatomic TT technique may considerably help patients.
Anterior Cruciate Ligament Reconstruction/methods , Anterior Cruciate Ligament/surgery , Finite Element Analysis , Tibia/surgery , Femur/surgery , Humans , Knee Joint/surgery , Models, Anatomic , Pressure , Range of Motion, Articular , Stress, Mechanical
To show the causal relationship between normal walking after various lateral ankle ligament (LAL) injuries caused by acute inversion ankle sprains and alterations in ankle joint contact characteristics, finite element simulations of normal walking were carried out using an intact ankle joint model and LAL injury models. A walking experiment using a volunteer with a normal ankle joint was performed to obtain the boundary conditions for the simulations and to support the appropriateness of the simulation results. Contact pressure and strain on the talus articular cartilage and anteroposterior and mediolateral translations of the talus were calculated. Ankles with ruptured anterior talofibular ligaments (ATFLs) had a higher likelihood of experiencing increased ankle joint contact pressures, strains and translations than ATFL-deficient ankles. In particular, ankles with ruptured ATFL + calcaneofibular ligaments and all ruptured ankles had a similar likelihood as the ATFL-ruptured ankles. The push off stance phase was the most likely situation for increased ankle joint contact pressures, strains and translations in LAL-injured ankles.
Ankle Injuries/physiopathology , Ankle Joint/physiopathology , Sprains and Strains/physiopathology , Walking/physiology , Adult , Finite Element Analysis , Humans , Male , Models, Biological
To evaluate the pre-stress in the menisci of a human knee joint, the technique of microindentation was adopted. Five specimens each for lateral and medial menisci attached to the tibia were prepared from the knee joints of Korean cadavers to represent the pre-stress state of the meniscus. To create test specimens for the stress-free state of the meniscus, each meniscus was resected from the tibia and cut into three parts, which were subsequently attached to a metal plate. Indentations were carried out in each meniscus in both the pre-stress state and the stress-free state. The pre-stresses in the menisci were evaluated using the load-versus-depth curves. Compressive pre-stresses were found in the menisci. For each indentation region, the pre-stresses in the medial meniscus were higher than in the lateral meniscus. The highest pre-stress in both the lateral and medial meniscus was found in the posterior regions, while the anterior regions experienced the lowest pre-stress. The obtained pre-stresses can be used for the accurate numerical analysis, the fabrication of artificial menisci, and the diagnosis of meniscal disease progression for human knee joints.
Biomechanical Phenomena/physiology , Knee Joint/physiology , Menisci, Tibial/physiology , Aged , Humans , Models, Biological
We used finite element (FE) method to investigate the effect of the drilling number and entry location of holes used in the multiple drilling technique on the stress and strain state in femur. Different three-dimensional FE models of a human hip joint with or without multiple drilling were fabricated using computed tomographic images obtained from the hip joint of a cadaver. The analysis technique was evaluated in a compression test using the cadaver specimen and FE analysis for the test using an FE model of the specimen. Von Mises stresses, principal stresses, and principal strains in the cancellous and cortical bone were calculated by using the different models, and changes in these values in relation to drilling number and entry hole locations were evaluated. Calculated peak values were much smaller than the yield strength, tensile strength, and yield strain of the cancellous and cortical bone for all cases of multiple drilling. Our results support that the multiple drilling technique for osteonecrosis of the femoral head is a stable operation technique.
Femur Head Necrosis/surgery , Finite Element Analysis , Aged , Femur Head/pathology , Femur Head/physiopathology , Femur Head/surgery , Femur Head Necrosis/physiopathology , Hip Joint/physiopathology , Humans , Male , Models, Biological , Stress, Mechanical
To investigate the effects of meniscectomy on degenerative osteoarthritis, a three-dimensional (3D) finite element (FE) model of the human lower limb is constructed from a combination of magnetic resonance (MR) images and computed tomographic (CT) images that can provide anatomically suitable boundary conditions for a knee joint. Four cases, i.e., the intact meniscus, and the partial, sub-total, and total meniscectomy of the medial meniscus are modeled and simulated. We consider that the cartilage-to-cartilage contact area and the peak contact pressure in the meniscus may be significant parameters in evaluating degenerative osteoarthritis. Partial meniscectomy can be regarded as a better treatment than sub-total/total meniscectomy, and a high possibility of degenerative osteoarthritis is anticipated after total meniscectomy. Moreover, medial meniscectomy has the potential to bring about degenerative osteoarthritis in both the medial compartment and the lateral compartment of a knee joint.
Knee Joint/surgery , Menisci, Tibial/surgery , Models, Biological , Osteoarthritis, Knee/etiology , Postoperative Complications/physiopathology , Adult , Biomechanical Phenomena , Finite Element Analysis , Humans , Knee Joint/physiopathology , Magnetic Resonance Imaging/methods , Male , Menisci, Tibial/physiopathology , Osteoarthritis, Knee/physiopathology , Tomography, X-Ray Computed/methods
To investigate the biomechanical effect of collars, finite element analyses are carried out through two hip joints that are implanted using collared and collarless stems, respectively, and an intact hip joint model. For the analyses, the sacrum, coxal bone, and the cancellous and cortical bones of a femur are modelled using finite elements based on X-ray computed tomographic images taken from a 27-year-old woman. From the results, it is found that a collar with perfect calcar contact prevents stem subsidence and decreases the proximal-lateral gap and the lateral stem tilting. Therefore, it can impart reasonable biomechanical stability for total hip arthroplasty. However, its low load transmission ability and increased stem tilting effect due to the imperfect contact between the collar and the calcar are found to be serious problems that need to be solved. Results of clinical follow-up are presented for supporting the computational results.
Arthroplasty, Replacement, Hip , Femur/anatomy & histology , Adult , Biomechanical Phenomena , Female , Femur/diagnostic imaging , Finite Element Analysis , Humans , Models, Anatomic , Tomography, X-Ray Computed
