The authors constructed a novel apparatus based on subharmonic ultrasound for the accurate imaging of closed cracks. Linear and nonlinear responses not only from the tip but also from other parts of cracks were observed in fundamental and subharmonic images, which were changed with varying closure stress. The subharmonic images always gave an accurate length of partially closed cracks, in contrast to the fundamental images in which the crack length was underestimated. Significant similarities in generation and resonance phenomena of subharmonic waves, acoustic emission, and the vibration of microbubbles are discussed.

We developed a novel imaging method, subharmonic phased array for crack evaluation (SPACE) based on subharmonic waves and a phased array algorithm, to measure closed-crack depth in the thickness direction. This implementation of SPACE used a LiNbO3 single-crystal transmitter to generate the intense ultrasound required for subharmonic generation and a phased array sensor as a receiver for focusing using delay laws. We applied SPACE to closed fatigue and stress corrosion cracks and found that the measurement error of SPACE in measuring crack depths was approximately 1 mm, while that in the conventional method was 20 mm in an extreme case. To establish the basis of SPACE, we propose the concept of localized subharmonic resonances (LSRs) and explain SPACE images as accumulations of LSRs. As an example of LSR, the Rayleigh-mode resonance of a crack is described. The similarities and differences between subharmonic waves at closed cracks and at microbubbles are also discussed.

Hypophosphatasia (HPP) is an inherited disease caused by a deficiency of tissue-nonspecific alkaline phosphatase (TNALP). The major symptom of human HPP is hypomineralization, rickets, or osteomalacia, although the clinical severity is highly variable. The phenotypes of TNALP knockout (Akp2

Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNALP) isozyme. The clinical severity of HPP varies widely, with symptoms including rickets and osteomalacia. TNALP knockout (Akp2−/−) mice phenotypically mimic the severe infantile form of HPP; that is, TNALP-deficient mice are born with a normal appearance but die by 20 days of age owing to growth failure, hypomineralization, and epileptic seizures. In this study, a lentiviral vector expressing a bone-targeted form of TNALP was injected into the jugular vein of newborn Akp2−/− mice. We found that alkaline phosphatase activity in the plasma of treated Akp2−/− mice increased and remained at high levels throughout the life of the animals. The treated Akp2−/− mice survived for more than 10 months and demonstrated normal physical activity and a healthy appearance. Epileptic seizures were completely inhibited in the treated Akp2−/− mice, and X-ray examination of the skeleton showed that mineralization was significantly improved by the gene therapy. These results show that severe infantile HPP in TNALP knockout mice can be treated with a single injection of lentiviral vector during the neonatal period. © 2011 American Society for Bone and Mineral Research.