With the aim of clinical applications of X-ray phase imaging based on Talbot–Lau-type grating interferometry to joint diseases and breast cancer, machines employing a conventional X-ray generator have been developed and installed in hospitals. The machine operation especially for diagnosing rheumatoid arthritis is described, which relies on the fact that cartilage in finger joints can be depicted with a dose of several milligray. The palm of a volunteer observed with 19 s exposure (total scan time: 32 s) is reported with a depicted cartilage feature in joints. This machine is now dedicated for clinical research with patients.

The mammalian skeleton stores calcium and phosphate ions in bone matrix. Osteocytes in osteocyte lacunae extend numerous dendrites into canaliculi less than a micron in diameter and which are distributed throughout bone matrix. Although osteoclasts are the primary bone-resorbing cells, osteocytes also reportedly dissolve hydroxyapatite at peri-lacunar bone matrix. However, robust three-dimensional evidence for peri-canalicular bone mineral dissolution has been lacking. Here we applied a previously reported Talbot-defocus multiscan tomography method for synchrotron X-ray microscopy and analyzed the degree of bone mineralization in mouse cortical bone around the lacuno-canalicular network, which is connected both to blood vessels and the peri- and endosteum. We detected cylindrical low mineral density regions spreading around canaliculi derived from a subset of osteocytes. Transmission electron microscopy revealed both intact and demineralized bone matrix around the canaliculus. Peri-canalicular low mineral density regions were also observed in osteopetrotic mice lacking osteoclasts, indicating that osteoclasts are dispensable for peri-canalicular demineralization. These data suggest demineralization can occur from within bone through the canalicular system, and that peri-canalicular demineralization occurs not uniformly but directed by individual osteocytes. Blockade of peri-canalicular demineralization may be a therapeutic strategy to increase bone mass and quality.

X-ray phase imaging that uses the phenomena of X-ray refraction and scattering to generate image contrast has the potential to overcome the drawback of conventional X-ray radiography in observing biological soft tissues. After its dawn at synchrotron radiation facilities 30 years ago, the development of X-ray phase imaging is expanding to hospitals by grating-based phase-imaging approaches available with a conventional X-ray tube. In this review, after introducing the physical advantages and methodological details of X-ray phase imaging, recent trials of instrumentation in hospitals for diagnoses of rheumatoid arthritis and chronic obstructive pulmonary disease are introduced.

An X-ray Talbot-Lau interferometer scanning setup consisting of three transmission gratings, a laboratory-based X-ray source that emits X-rays vertically, and an image detector on the top has been developed for the application of X-ray phase imaging to moving objects that cannot be tested clearly with conventional absorption contrast. The grating-based X-ray phase imaging method usually employs a phase-stepping (or fringe-scanning) technique by displacing one of the gratings step-by-step while the object stays still. Since this approach is not compatible with a scanner-type application for moving objects, we have developed a new algorithm for achieving the function of phase-stepping without grating displacement. By analyzing the movie of the moiré pattern as the object moves across the field of view, we obtain the absorption, differential phase, and visibility images. The feasibility of the X-ray phase imaging scanner has been successfully demonstrated for a long sample moving at 5 mm/s. This achievement is a breakthrough for the practical industrial application of X-ray phase imaging for screening objects carried on belt-conveyers such as those in factories.

Under the JST-ERATO project in progress to develop X-ray and neutron phase-imaging methods together, recent achievements have been selected and reviewed after describing the merit and the principle of the phase imaging method. For X-ray phase imaging, recent developments of four-dimensional phase tomography and phase microscopy at SPring-8, Japan are mainly presented. For neutron phase imaging, an approach in combination with the time-of-flight method developed at J-PARC, Japan is described with the description of new Gd grating fabrication.

Endochondral ossification is a developmental process by which cartilage is replaced by bone. Terminally differentiated hypertrophic chondrocytes are calcified, vascularized, and removed by chondroclasts before bone matrix is laid down by osteoblasts. In mammals, the malleus is one of three auditory ossicles that transmit vibrations of the tympanic membrane to the inner ear. The malleus is formed from a cartilaginous precursor without growth plate involvement, but little is known about how bones of this type undergo endochondral ossification. Here, we demonstrate that in the processus brevis of the malleus, clusters of osteoblasts surrounding the capillary loop produce bone matrix, causing the volume of the capillary lumen to decrease rapidly in post-weaning mice. Synchrotron X-ray tomographic microscopy revealed a concentric, cylindrical arrangement of osteocyte lacunae along capillaries, indicative of pericapillary bone formation. Moreover, we report that overexpression of Fosl1, which encodes a component of the AP-1 transcription factor complex, in osteoblasts significantly blocked malleal capillary narrowing. These data suggest that osteoblast/endothelial cell interactions control growth plate-free endochondral ossification through ‘osteogenic capillaries’ in a Fosl1-regulated manner.