Background:Histopathological evaluation of lung biopsy specimens is inherently destructive and reduces the three-dimensional tissue architecture to limited two-dimensional sections. For small bronchoscopic specimens, this may compromise the optimal tissue utilization for diagnosis and molecular testing. We investigated whether synchrotron-based phase-contrast X-ray computed tomography (CT) could be used to non-destructively visualize the three-dimensional architecture of clinically obtained transbronchial cryobiopsy specimens. Methods:In this exploratory imaging study, we prospectively enrolled patients with peripheral pulmonary lesions who underwent bronchoscopy. An additional single cryobiopsy specimen was obtained and imaged using synchrotron-based phase-contrast CT. The structural features were evaluated by three blinded observers using predefined ordinal scores. Interobserver agreement was assessed using the weighted kappa and intraclass correlation coefficients. Representative cases underwent serial histological sectioning, and exploratory slow-freezing micro-CT imaging was performed on a subset. Results:Fifteen patients were included. Phase-contrast CT revealed major structural features including alveolar-like airspaces, tissue density, glandular lumina, solid nest-like structures, thickened bronchial wall structures, and calcified foci. The imaging findings generally corresponded to the histological findings. Interobserver agreement was moderate to substantial for airspace preservation and tissue density, whereas agreement was poor for glandular and solid nest-like structures. Exploratory micro-CT showed partial visualization of finer structures but was limited by image blurring and distortion. Conclusions:Synchrotron-based phase-contrast CT enabled non-destructive three-dimensional structural visualization of clinically obtained transbronchial cryobiopsy specimens. Although the current resolution remains insufficient for detailed histological classification, this study represents a proof-of-concept for the feasibility of this imaging technique rather than a clinical workflow utility.
The Silicon-On-Insulator PIXel (SOIPIX) detector is a unique monolithic structure imaging device currently being developed by the SOIPIX group, led by the High Energy Accelerator Research Organization (KEK). Our detector team at the KEK Photon Factory (PF) has developed an X-ray camera based on the INTPIX4NA SOIPIX detector. This detector provides a sensitive area of 14.1 × 8.7 mm2, with 425,984 pixels arranged in an 832-column × 512-row matrix and a pixel size of 17 × 17 µm2, and offers high spatial resolution and excellent sensitivity under low-intensity X-ray conditions. The readout system used in the X-ray camera is developed at the PF. It is equipped with SiTCP-XG, a 10 Gb Ethernet network controller implemented on a field-programmable gate array, enabling high-frame-rate imaging at several hundred hertz. We are currently investigating the applicability of this X-ray camera in several experiments at KEK. Herein, we report three recent application studies: (1) X-ray zooming microscope optics using two Fresnel zone plates at PF AR-NE1A; (2) phase-contrast X-ray imaging system using a two-crystal X-ray interferometer at PF BL-14C; and (3) nondestructive lithium detection in Li-ion battery electrode materials using muonic X-rays at J-PARC MLF Muon D2.
Mechanical forces caused by fetal movements are essential for normal musculoskeletal development. However, the relationship between skeletal development and knee joint motion in utero remains unclear. We aimed to clarify the development of lower limb musculoskeletal structures during the embryonic and early fetal stages from a kinematic perspective and to compare muscle and skeletal developmental processes. We analyzed 29 human embryonic and fetal specimens. Using phase-contrast X-ray computed tomography and magnetic resonance imaging, we analyzed the morphogenesis of the knee joint components, trochlear groove angle, and hypothetical joint motion of the thigh muscles in three dimensions. To analyze chronological morphogenesis, Procrustes analysis was performed, and Principal component analysis and linear discriminant analysis were subsequently conducted using the Procrustes coordinates. The trochlear groove angle on the plane vertical to the femoral axis decreased from approximately 160° to 130° until 120 mm Crown-rump length (CRL) and remained constant until 185 mm CRL. All hypothetical joint motions increased slowly between 30 and 100 mm CRL, whereas rapidly after approximately 100 mm CRL. The protrusions of the lateral femoral condyle became more pronounced from fetal stage as they grew. The timing of the onset of fetal movement and the increase in muscle mass and joint motion during early pregnancy were consistent with those of previous studies, and the timing of the angle stabilization occurred almost simultaneously with the rapid increase in femoral muscle mass and hypothesized joint motion. It suggested that stabilization of joint morphology enables smooth joint motion, which leads to an increase in muscle mass and joint motion.
The texture of Japanese wheat noodles (somen) is strongly influenced by salt addition; however, its effect on internal water penetration during boiling and subsequent soaking has not been directly visualized. This study aimed to clarify how salt-induced differences in internal microstructure govern water penetration and texture formation of somen. Synchrotron radiation-based micro-computed tomography (micro-CT) combined with a bromine-based contrast agent was used to visualize water distribution. Salted (S) and salt-free (SF) somen produced under identical conditions were compared in terms of physical properties, salt elution, microstructure, and water penetration behavior. SF somen exhibited higher hardness and elastic firmness during the early stages of boiling. Micro-CT analysis revealed that S somen possessed a denser and more continuous matrix with fewer but larger pores, whereas SF somen exhibited a highly porous structure composed of numerous small pores. Contrast-enhanced imaging demonstrated faster and more uniform water penetration in S somen, while water penetration was delayed in SF somen. These results indicate that salt promotes structural continuity, facilitating internal water transport and influencing post-boiling texture formation. This study demonstrates the utility of synchrotron micro-CT for linking internal structure, water dynamics, and physical properties in noodle products.
The origin of the vertebrate jaw is one of the most long-standing and enigmatic topics in vertebrate evolution. To address this fundamental problem, lamprey larvae have long been the primary source of information on the cranial system of jawless vertebrates. However, their cranial anatomy remains contentious, largely because previous anatomical studies have relied primarily on conventional methodologies, leaving room for subjective identification. Here, we focused on cranial muscles whose morphology and innervation have been particularly controversial, performing high-resolution and objective imaging of the muscles and trigeminal nerve branches in three dimensions using various advanced techniques, including micro-computed tomography and light-sheet microscopy. Our detailed observations revealed several key characters that have previously been overlooked. First, an undescribed upper lip muscle is innervated by a sub-branch of the second major branch of the trigeminal nerve, which had long been thought to be purely sensory. Second, most lower lip muscles exhibit dual innervation by the second and third major branches of the trigeminal nerve. Last, the topographical arrangement of the lower lip muscle was elucidated in detail for the first time, suggesting that this muscle gives rise to the musculature of adult lingual apparatus through metamorphosis. Our three-dimensional data revises previous views on the cranial morphology of lamprey larvae and provides a solid foundation for comparative morphological and developmental studies across extinct and extant vertebrates. In addition, the cutting-edge imaging methods employed here could be applied to metamorphic and adult lampreys, offering a promising approach for elucidating the morphogenesis of the adult head. Taken together, this study opens new avenues for evolutionary developmental and paleontological research on the early evolution of vertebrate heads.
X-ray computed tomography (CT) is widely used in various fields for the non-destructive three-dimensional (3D) observation of internal structures within objects. However, biological cells are primarily composed of light elements such as oxygen and carbon, which have high X-ray transmittance. Consequently, conventional absorption contrast X-ray CT is unable to achieve fine 3D observations of such specimens. We hereby present a technique of novel contrast improvement, the slow freezing contrast improvement method. This method utilizes the aggregation of solutes during slow freezing of aqueous solutions to increase contrast. As plant cells are slowly cooled, intracellular fluid crystallizes, concentrating sugars in specific areas. This process allows for micron-scale visualization of cell structures without staining, using conventional absorption contrast X-ray CT. Experiments on slowly frozen fruits and formalin-fixed mouse organs using synchrotron-based cryo micro-X-ray CT produced high-resolution images of cellular structures. The ice crystal patterns formed within cells varied based on sugar concentration, suggesting potential for detecting sugar levels in individual cells. This method shows promise as a third approach for fine 3D observation of biological cells, complementing contrast agent and phase-contrast imaging techniques.
Crystallization and dissociation are among the most prominent phenomena in condensed matter science, but understanding from a microscopic perspective, such as impurities in natural materials such as gas hydrates, is fragmented.
The morphology of the ankle joint and foot during early development exhibits distinct differences from that observed in adults, with physiological clubfoot being a well-documented phenomenon. To better understand this posture and its transformation, the skeletal elements in this region were three-dimensionally reconstructed using high-resolution phase-contrast x-ray computed tomography and magnetic resonance imaging of specimens (n = 23) during the late embryonic and early fetal periods, before joint cavity formation. Sequential changes were analyzed both morphologically and morphometrically from anterior, lateral, posterior, and plantar views. The reduction in plantar flexion of the ankle joint rendered the positional change of the hindfoot substantially more complex, and three-dimensional reconstruction facilitated its comprehension. Continuous supination of the hindfoot, pronation of the forefoot along the foot axis, and reduced plantar flexion of the ankle joint were identified as key postural changes that contributed to the development of temporal physiological clubfoot, initiated as early as the late embryonic period. Twisting between the forefoot and hindfoot and the abduction of the ankle joint, resulting from the obliquity of the tibia-talus joint, were substantial. The offset effect of the two angle changes conceals such changes in most previous studies. Changes in the shape of the tarsal bones, especially the calcaneus and talus, affected the relative bone positions, indicating that the concept of "differential growth" may apply to ankle-joint and foot morphogenesis. Findings of the present study are expected to enhance understanding of the pathogenesis and mechanisms underlying clubfoot and facilitate fetal diagnosis via morphological assessments.
HASClay, a porous material designed for heat storage and dissipation, efficiently utilizes low-temperature waste heat below 100°C. In this study, its internal density structure and moisture adsorption–desorption behavior were investigated using synchrotron radiation–based X-ray computed tomography (CT). X-ray CT analysis revealed distinct high- and low-density regions within HASClay, with the density of both regions increasing as moisture content increased due to water vapor adsorption. In addition, the morphology and distribution of these regions varied depending on the product associated with the temperature during synthesis. Because high-density regions adsorb moisture more efficiently than low-density regions, it was suggested that a key design strategy for improving HASClay is to increase the proportion of high-density regions. Furthermore, HASClay samples subjected to repeated moisture adsorption–desorption cycles exhibited reduced moisture desorption capacity compared with fresh samples. These findings demonstrate that X-ray CT is an effective technique to reveal the water vapor adsorption and desorption process of HASClay based on changes in the internal density distribution.
In this study, we observed natural methane (CH4) hydrate sediments, which are a type of unconventional natural gas resources, using x-ray computed tomography (CT). Because CH4 hydrates are formed by hydrogen bonding of water molecules with CH4, material decomposition becomes challenging when CH4 hydrates coexist with liquid or solid water in natural sediments. Tri-contrast (absorption, refraction, and scattering) imaging was performed via diffraction enhanced x-ray CT optics using monochromatic synchrotron x rays. The quantitative characterization of the contrast changes successfully enabled the decomposition of CH4 hydrates coexisting with frozen seawater (ice) in natural sediments obtained from the Okhotsk Sea. This study reveals complementary structural information about the microtexture and spatial relation among CH4 hydrates, ice, and pores by utilizing the distinct physical properties of x rays when passing through the materials. These results highlight the exceptional capabilities of high-resolution multicontrast x-ray tomography in materials science and geoscience applications.
Developing highly efficient methane (CH4) hydrate storage methods and understanding the hydrate dissociation kinetics can contribute to advancing CH4 gas storage and transport. The effects of tetrabutylammonium bromide (TBAB) (a thermodynamic promoter) addition on the kinetics of CH4 hydrate were evaluated on the microscopic scale using synchrotron x-ray computed tomography (CT) and powder x-ray diffraction. Microscopic observations showed that a 5 wt. % TBAB solution facilitated the nucleation of CH4 hydrate owing to the initial growth of TBAB semi-clathrate hydrate particles. The CH4 hydrate crystals in the CH4 + TBAB hydrate sample were sponge-like with many internal pores and exhibited slightly enhanced self-preservation compared to the pure CH4 hydrate, both in the bulk and after pulverization to a fine powder. This study demonstrates the feasibility of controlling the rate of CH4 hydrate formation and preservation by using aqueous TBAB solutions in CH4 hydrate formation.
During the fetal period, oxygenated blood from the placenta flows through the umbilical vein (UV), portal sinus, ductus venosus (DV), and inferior vena cava (IVC) to the heart. This venous route varies regionally in many aspects. Herein, we sought to characterize the venous route's morphological features and regional differences during embryonic and early-fetal periods. Twenty-nine specimens were selected for high-resolution digitized imaging; 18 embryos were chosen for histological analysis. The venous route showed a primitive, large, S-shaped curved morphology with regional narrowing and dilation at Carnegie stage (CS) 15. Regional differences in vessel-wall differentiation became apparent from approximately CS20. The vessel wall was poorly developed in most DV parts; local vessel-wall thickness at the inlet was first detected at CS20. The lumen of the venous route changed from a nonuniform shape to a relatively round and uniform morphology after CS21. During the early-fetal period, two large bends were observed around the passage of the umbilical ring and at the inlet of the liver. The length ratio of the extrahepatic UV to the total venous route increased. The sectional area gradually increased during embryonic development, whereas differences in sectional area between the DV, UV, and IVC became more pronounced in the early-fetal period. Furthermore, differences in the sectional area between the narrowest part of the DV and other hepatic veins and the transverse sinus became more pronounced. In summary, the present study described morphological, morphometric, and histological changes in the venous route throughout embryonic and early-fetal development, clarifying regional characteristics.
Government policies in the United States and the European Union promote standardization and value creation in the use of FAIR (findability, accessibility, interoperability, and reusability) data, which can enhance trust in digital health systems and is crucial for their success. Trust is built through elements such as FAIR data access, interoperability, and improved communication, which are essential for fostering innovation in digital health technologies. This Viewpoint aims to report on exploratory research demonstrating the feasibility of testing a patient-centric data flow model facilitating semantic interoperability on precision medical information. In this global trend, the interoperable interface called Sync for Science-J (S4S-J) for linking electronic medical records (EMRs) and personal health records was launched as part of the Basic Policy for Economic and Fiscal Management and Reform in Japan. S4S-J controls data distribution consisting of EMR and patient-generated health data and converts this information into QR codes that can be scanned by mobile apps. This system facilitates data sharing based on personal information beliefs and unlocks siloed Internet of Things systems with a privacy preference manager. In line with Japanese information handling practices, the development of a mobile cloud network will lower barriers to entry and enable accelerated data sharing. To ensure cross-compatibility and compliance with future international data standardization, S4S-J conforms to the Health Level 7 Fast Health Care Interoperability Resources standard and uses the international standardized logical observation identifiers names and codes (LOINC) to redefine medical terms used in different terminology standards in different medical fields. It is developed as an applied standard in medical information intended for industry, health care services, and research through secondary use of data. A multicenter collaborative study was initiated to investigate the effectiveness of this system; this was a registered, multicenter, randomized controlled clinical trial, the EMBRACE study of the mobile health app M♡Link for hyperglycemic disorders in pregnancy, which implements an EMR–personal health record interoperable interface via S4S-J. Nevertheless, the aforementioned new challenges, the pivotal Health Level 7 Fast Health Care Interoperability Resources system, and LOINC data mapping were successfully implemented. Moreover, the preliminary input of EMR-integrated patient-generated health data was successfully shared between authorized medical facilities and health care providers in accordance with the patients’ preferences. The patient-centric data flow of the S4S-J in Japan is expected to guarantee the right to data portability, which promotes the maximum benefit of use by patients themselves, which in turn contributes to the promotion of open science.
Elastography is a technique to assess the elastic properties of tissues and is currently used for diagnostics. In shear wave elastography, the elastic properties of tissue are estimated by finding propagation velocities of shear waves induced by external stimuli. Ultrasound imaging, magnetic resonance imaging, and X-ray imaging can be used to measure tissue displacements caused by shear waves. X-ray imaging may enable assessment of elastic properties at deep locations with high spatial resolution due to its short wavelength. We demonstrated three-dimensional X-ray elastography on an agarose gel sample. Firstly, we took projection images of the sample at a vibration frequency of 100 Hz with a detector frame rate of 10,000 fps while rotating the sample at pi rad/s. Next, three-dimensional images were reconstructed from projection images which were taken at the same phases of the vibration. Totally 100 three-dimensional images were reconstructed. The displacements were then calculated by a non-rigid registration method. Finally, we obtained storage and loss moduli by using an algebraic inversion of the differential equation method, which derives the elastic moduli from differential wave equations.
This study was undertaken to translate the Standardised Assessment of Personality – Abbreviated Scale (SAPAS) into Japanese and to evaluate its validity and reliability. SAPAS is one of the most rapid tools for assessing personality disorder (PD) and has excellent sensitivity and good specificity, whereas other PD assessment tools require such a significant investment of time that they are infeasible for large surveys or routine clinical practice. Customary assessment in clinical practice ideally incorporates screening for PD, as it is associated with a substantial public health burden, including premature mortality and increased health service utilization. Furthermore, PD’s status as a key prognostic variable of mental disorders also drives PD screening. While SAPAS has been translated into several languages, there has been no Japanese version. Therefore, we translated SAPAS into Japanese (SAPAS-J) and evaluated its reliability and validity. Study 1 recruited undergraduates to reveal its test–retest reliability. Although its internal consistency was not high, since the intent of the original SAPAS was to assess the broad character of personality disorder with the fewest possible items, minimal correlations between items were reasonable. We tested two factorial models, the single-factor model and the higher-order-single-factor model, and the latter offered better fitting. This higher-order model contained a three-factor structure corresponding to clusters described in DSM-5. It measures general PD traits as a common higher-order latent variable comprising those factors. Correlations of SAPAS-J with the much longer PD screening questionnaire in Study 1 and depressive and anxiety symptoms in Study 2 from the general population support its validity. Although validation for the clinical use of SAPAS-J is limited, our research with non-clinical populations demonstrated sufficient validity to justify its use in the context of psychopathological analog research. Since PD is understood as a continuum, the severity of which is distributed dimensionally, the analog study recruiting from the general population and attempting to reveal psychopathological mechanisms of PD is meaningful.
We used 3D micro-X-ray topography (3D mu-XRT) to construct a 3D structure of the threading screw dislocations (TSDs) in 4H-SiC. The 00012 diffraction condition, which can observe the strain field at a deep location in the sample, was employed in the 3D mu-XRT geometry. The dislocation core-lines of TSDs propagating from the surface to the interior of the sample were successfully captured spatially, and TSDs parallel to and inclined from the 0001 axis were both confirmed. Either the component 1 over bar 1 over bar 20 or 1 over bar 100 of the Burgers vector is considered to be mixed in the inclined TSD. To verify this suggestion, scanning electron microscopy (SEM) and cathodoluminescence (CL) spectroscopy were performed on the molten-alkali-etched TSDs. Both the SEM shapes and CL intensities of the TSD etch pits with inclination showed the features of the mixed component, supporting the correlation between the inclination and mixed component in TSD.
The left atrium wall has several origins, including the body, appendage, septum, atrial-ventricular canal, posterior wall, and venous component. Here, we describe the morphogenesis of left atrium based on high-resolution imaging (phase-contrast X-ray computed tomography and magnetic resonance imaging). Twenty-three human embryos and 19 fetuses were selected for this study. Three-dimensional cardiac images were reconstructed, and the pulmonary veins and left atrium, including the left atrial appendage, were evaluated morphologically and quantitatively. The positions of the pericardial reflections were used as landmarks for the border of the pericardial cavity. The common pulmonary vein was observed in three specimens at Carnegie stages 17-18. The pericardium was detected at the four pulmonary veins (left superior, left inferior, right superior, and right inferior pulmonary veins) at one specimen at Carnegie stage 18 and all larger specimens, except the four samples. Our results suggest that the position of the pericardial reflections was determined at two pulmonary veins (right and left pulmonary vein) and four pulmonary veins almost simultaneously when the dorsal mesocardial connection between the embryo and heart regressed. The magnetic resonance images and reconstructed heart cavity images confirmed that the left atrium folds were present at the junction between the body and venous component. Three-dimensional reconstruction showed that the four pulmonary veins entered the dorsal left atrium tangentially from the lateral to the medial direction. More specifically, the right pulmonary veins entered at a greater angle than the left pulmonary veins. The distance between the superior and inferior pulmonary veins was shorter than that between the left and right pulmonary veins. Three-dimensional reconstruction showed that the venous component increased proportionally with growth. No noticeable differences in discrimination between the right and left parts of the venous component emerged, while the junction between the venous component and body gradually became inconspicuous but was still recognizable by the end of the observed early fetal period. The left superior pulmonary vein had the smallest cross-sectional area and most flattened shape, whereas the other three were similar in area and shape. The left atrial appendage had a large volume in the center and extended to the periphery as a lobe-like structure. The left atrial appendage orifice increased in the area and tended to become flatter with growth. The whole left atrium volume<^>(1/3) increased almost proportionally with growth, parallel to the whole heart volume. This study provided a three-dimensional and quantitative description of the developmental process of the left atrium, comprising the venous component and left atrial appendage formation, from the late embryonic to the early fetal stages.
There has been growing interest in the use of hydrate-based technology for energy and environmental applications; however, structural characterization of some hydrate phases relevant to these applications has not been dealt with sufficiently in previous studies. This paper reports crystallographic characterization of hydrates formed in [CO2 + 1-propanol (propan-1-ol) + water] and [CO2 + 2-propanol (propan-2-ol) + water] systems with powder X-ray diffraction (PXRD) and X-ray computed tomography (CT) measurements. It was revealed that structure I CO2 hydrate and a non-crystalline phase involving 1-propanol are formed in CO2 + 1-propanol system. As for CO2 + 2-propanol system, crystalline structure of the formed hydrate differs depending on thermodynamic conditions; at 3.3 MPa, 274 K and at 2.2 MPa, 263 K, sI CO2 hydrate was formed, whereas at lower pressure and temperature, i.e., 0.5 MPa and 255 K, a new tetragonal structure outside the canonical hydrates was identified. Implications of using 1-propanol as a thermodynamic inhibitor and kinetic promoter of hydrate formation are discussed, which opens some possibilities into petroleum exploration/production applications and the development of hydrate-based refrigeration systems. The structural identification of tetragonal (sII ') CO2 + 2propanol hydrate sheds new light on developing hydrate-based CCS process and novel skin care products.