Optimizing irradiation conditions for low-intensity pulsed ultrasound to upregulate endothelial nitric oxide synthase.

PURPOSE: Here we aimed to develop a minimally invasive treatment for ischemic heart disease and demonstrate that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia by promoting myocardial angiogenesis in a porcine model of chronic myocardial ischemia. Studies to date determined the optimal treatment conditions within the range of settings available with existing ultrasound equipment and did not investigate a wider range of conditions. METHODS: We investigated a broad range of five parameters associated with ultrasound irradiation conditions that promote expression of endothelial nitric oxide synthase (eNOS), a key molecule that promotes angiogenesis in human coronary artery endothelial cells (HCAEC). RESULTS: Suboptimal irradiation conditions included 1-MHz ultrasound frequency, 500-kPa sound pressure, 20-min total irradiation time, 32-48-[Formula: see text] pulse duration, and 320-[Formula: see text] pulse repetition time. Furthermore, a proposed index, [Formula: see text], calculated as the product of power and the total number of irradiation cycles applied to cells using LIPUS, uniformly revealed the experimental eNOS expression associated with the various values of five parameters under different irradiation conditions. CONCLUSION: We determined the suboptimal ultrasound irradiation conditions for promoting eNOS expression in HCAEC.

Evaluation of local changes in radio-frequency signal waveform and brightness caused by vessel dilatation for ascertaining reliability of elasticity estimation inside heterogeneous plaque: a preliminary study.

PURPOSE: To diagnose plaque characteristics, we previously developed an ultrasonic method to estimate the local elastic modulus from the ratio of the pulse pressure to the strain of the arterial wall due to dilatation in systole by transcutaneously measuring the minute thinning in thickness during one cardiac cycle. For plaques, however, some target regions became thicker as the vessel dilates, resulting in false elasticity. Therefore, a method to identify a reliable target for the elastic modulus estimation is indispensable. As a candidate for an identification index of plaques that become thicker during one cardiac cycle, the correlation of the radio-frequency (RF) signals remains high and it is not sufficient to obtain the elasticity. In this study, we thoroughly observed the target with a high correlation but positive strain in the plaque and characterized it by the property of the surrounding area. METHODS: For the plaque formed in the right carotid sinus of a patient with hyperlipidemia and the wall of the right common carotid artery of a young healthy male, (1) the correlation value as the similarity between the RF signals, (2) change in brightness obtained from the log-compressed envelope signals, and (3) strain obtained between the time of the R-wave and that of the maximum vessel dilatation were observed to characterize the region in the plaque. RESULTS: In the plaque, it was found that the region with high correlation and positive strain and its surrounding area could be classified into one of the three typical patterns. CONCLUSION: As a preliminary study, this study provides a clue to assert the reliability of elasticity estimates for a region with high correlation and positive strain in the plaque based on measurable properties.

Development of an ultrasound microscope combined with optical microscope for multiparametric characterization of a single cell.

Biomechanics of the cell has been gathering much attention because it affects the pathological status in atherosclerosis and cancer. In the present study, an ultrasound microscope system combined with optical microscope for characterization of a single cell with multiple ultrasound parameters was developed. The central frequency of the transducer was 375 MHz and the scan area was 80 × 80 µm with up to 200 × 200 sampling points. An inverted optical microscope was incorporated in the design of the system, allowing for simultaneous optical observations of cultured cells. Two-dimensional mapping of multiple ultrasound parameters, such as sound speed, attenuation, and acoustic impedance, as well as the thickness, density, and bulk modulus of specimen/cell under investigation, etc., was realized by the system. Sound speed and thickness of a 3T3-L1 fibroblast cell were successfully obtained by the system. The ultrasound microscope system combined with optical microscope further enhances our understanding of cellular biomechanics.