This paper describes new measurement techniques developed at National Metrology Institute of Japan (NMIJ) required for high-intensity therapeutic ultrasound (HITU). The first is ultrasonic power measurement higher than 15 W by using a calorimetric method. With this method, ultrasonic power measurement for HITU has been achieved up to 100 W. We already established an ultrasonic power standard in 2005 by using “radiation force balance” between 1 mW to 15 W. Additionally, we started a calibration service in 2014 at a range of 15 W to 100 W using the calorimetric method. In this article, a new method for ultrasonic power measurement with the calorimetric method that uses water as the heating material is described. The second technique proposed is the quantitative measurement of the amount of generated cavitation by applying a “cavitation sensor.” The measured value, namely Broadband integrated voltage (BIV), which is calculated from the cavitation sensor signal, has been compared with two different conventional methods for measuring the amount of cavitation. The data measured using the cavitation sensor and conventional methods showed a linear relation. These results indicate that the cavitation sensor can be used as a tool for quantitative measurement. In future, a calibration method should be established for the cavitation measurement tool.

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Recently, a number of diagnosis and treatment methods employing high-intensity ultrasound have been developed and used clinically. However, it is important from the standpoint of protecting human tissue and the standpoint of effective utilization of high-intensity ultrasound to accurately measure sound field, sound pressure, and acoustic intensity. Thus, we have been developing an anti-cavitation hydrophone that can withstand measurement in a high-intensity ultrasound field with inertial acoustic cavitation by deposition of a hydrothermally synthesized lead zirconate titanate (PZT) poly-crystalline film on the reverse side of the titanium front plate. However, our conventional anti-cavitation hydrophone with low specific acoustic impedance backing had limitations, i.e., the receiving sensitivity decreased with an increase in frequency, and it could not describe the actual ultrasound waveform with high fidelity. Therefore, we considered improving the frequency characteristics of the receiving sensitivity by performing numerical simulations based on the Mason’s equivalent circuit model and one-dimensional acoustic transmission line model. It was found that flat frequency characteristics of the receiving sensitivity could be obtained by using a backing with about 20 MRayl specific acoustic impedance. We then developed a new anti-cavitation hydrophone using a backing with about 20 MRayl specific acoustic impedance based on the simulated results. The decrease in receiving sensitivity in the high-frequency range could be suppressed in our newly fabricated anti-cavitation hydrophone. Furthermore, durability tests of each hydrophone under ultrasound exposure were performed in a water tank containing ultrasound cleaner with generation of inertial acoustic cavitation. It was found that our new anti-cavitation hydrophone had a 10-fold longer lifetime as compared with a commercial needle-type hydrophone.

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Currently, ultrasound diagnostic devices are widely used and have become an essential tool in the medical front, particularly in the field of obstetrics and gynecology. These diagnostic devices have high frequencies and a large power of irradiated ultrasound waves for improving their performance and expanding the fields of their application, but lately research is being conducted worldwide to verify the safety of these devices. At the Japan Society of Ultrasonics in Medicine (JSUM), the Ultrasound Equipment and Safety Committee is testing and verifying the safety of these devices. In recent years, JSUM has been examining imaging equipment that use acoustic radiation force from the perspective of their impact on human health. With this background in mind, we developed a thermal imaging-based measurement system that uses infrared cameras to measure the two-dimensional temperature distributions of cross-sections of a phantom prepared following IEC 60601-2-37. We first obtained the relationship between the temperature distribution and irradiated ultrasound output power. We also conducted temperature rise tests on the propagation direction of ultrasound waves for cases with and without a mimicking bone (acrylic). Hence, we were able to visualize the effect of the temperature rise on the bone and neighboring areas caused by the reflection of ultrasonic waves. Next, we examined the validity of thermal imaging by comparing these measurements with those obtained through the conventional thermocouple method. We further examined their validity by conducting numerical simulations and comparing the simulation results with the thermal imaging measurement results. We consider that developing an easy-to-use simulation program will enable technicians to predict the temperature distribution in the body and help raise awareness of safety.

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Three optical techniques for visualizing ultrasound acoustic fields used for medical applications are described. The first technique is a type of shadowgraphy that can be realized using a simple optical system consisting of only a point light source and a camera. Characteristics of the images acquired using this technique are compared to those acquired using the Schlieren technique, and the advantage of this technique is demonstrated by visualization of an acoustic field of diagnostic short-pulsed ultrasound. The other two techniques are quantitative shadowgraphy and the phase-contrast technique. These techniques are designed for visualization of three-dimensional (3D) pressure distributions to replace hydrophone measurements. Their principles are explained in detail, and experimental results for visualization of a focused ultrasound field are discussed. The acquired images were quantitatively investigated with comparison to hydrophone measurements, demonstrating the usefulness of the techniques in quantitative evaluation of 3D ultrasound fields.

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Purpose: We propose a crossed beam contrast echo (CBCE) method, where the measurement of blood flow is achieved by analyzing the sum- or different-frequency components generated by nonlinear vibration of microbubbles under the radiation of two ultrasonic beams with different frequencies. This method allows us to measure only blood flow velocity separate from motion of biological soft tissue without using a high-pass filter such as MTI filter, because the sum- or different-frequency components can increase the contrast echo to tissue echo ratio (CTR). In this paper, we demonstrate the measurement of only blood flow velocity and show the advantage of this method. Subjects and Methods: In an experimental system comprised of steady flow with flow volume of approximately 126 mm³/s, we employed the CBCE method to measure the flow velocity. A commercially available contrast agent, Sonazoid, was injected into the channel surrounded by a gel phantom mimicking tissue. The flow velocity was evaluated by Doppler shift of fundamental, second harmonic, and sum-frequency components. Results and Discussion: CTR of the sum-frequency component was larger than that of the fundamental and second harmonic components when the echo signal from microbubbles was overlapped with that of the gel phantom in the range gate. The flow velocity measured by using the sum-frequency component was consistent with the reference value as compared with the fundamental and second harmonic components. Conclusion: In the CBCE method, the improvement of CTR with the sum-frequency component enables us to better evaluate the precious flow velocity as compared with other frequency components.

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Purpose: As basic studies to realize in vivo sonoporation, rates of cell membrane damage during sonoporation were evaluated using monolayer cells cultured on scaffolds withdifferent degrees of stiffness. Methods: Four types of scaffolds, constructed using collagen gel, 10 and 30% acrylamide gels, and a coverslip, were used for cultivation of monolayer cells. Young’s moduli measured using an atomic force microscope were in the range 0.09-8.6 kPa for the gel scaffolds, whereas Young’s modulus for living cells was 4.5 kPa. Cells with attached microbubbles were exposed to one-shot pulsed ultrasound of 8.0/-1.3 MPa in peak positive/negative pressures with durations of 3, 100, and 10,000 cycles. Results: Cell membrane damage was visualized by fluorescence microscopy using propidium iodide. The 3-cycle ultrasound pulse had no significant effect; however, the rates of damage caused by 100-cycle and 10,000-cycle pulses showed a strong tendency for higher rates of damage with a higher Young’s modulus. Conclusion: The experimental results indicate that the stiffness of the underlying layer of adherent cells should be considered as an essential parameter of the sonoporation condition and that the optimum exposure conditions for in vivo sonoporation should be determined with consideration of the physical properties of underlying tissues.

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Purpose: Vortex formation in the left ventricle(LV) can be visualized by novel vector flow mapping (VFM) based on color Doppler and speckle tracking data. The aim of this study was to evaluate the impact of a vortex during the ejection period using VFM. Subjects and methods: Color Doppler images were obtained to produce VFM images in 80 subjects (20 normal, 29 with dilated cardiomyopathy, and 31 with old myocardial infarction). The duration of the LV vortex was measured and expressed as the ratio to the ejection time (VTRe). Results: The VTRe showed significant correlations with EDV (ρ= 0.672, p < 0.001), ESV (ρ= 0.772, p < 0.001), EF (ρ=-0.783, p < 0.001), left atrium diameter (LAd) (ρ= 0.302, p = 0.007), stroke volume (ρ=-0.600, p < 0.001), e’ (ρ=-0.389, p < 0.001), a’ (ρ=-0.314, p = 0.005), s’ (ρ=-0.512, p < 0.001), and E/e’ (ρ= 0.330, p = 0.003). The diastolic parameters (e’, a’, E/e’, LAd) were not correlated when they were adjusted by EF. Conclusions: In the normal LV, a vortex existed for only a limited time during the early ejection period. In contrast, the lower the EF was, the longer the vortex remained during systole. Evaluation of vortices by VFM may noninvasively provide novel insights into the pathophysiology of impaired cardiac function.

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A woman in her 70s was admitted with progressive dyspnea on exertion. She had abnormal levels of serum ferritin and was diagnosed with sideroblastic anemia with hepatic hemochromatosis based on chemical study and liver biopsy 2 years previously. She showed marked elevation of serum ferritin levels (3,210 ng/ml), cardiomegaly on chest X-p, conduction disturbance on electrocardiography, and high intensity of the left and right ventricular walls on plain chest CT indicating myocardial iron deposition. Echocardiography on admission revealed diffuse left ventricular hypokinesis (ejection fraction 35%) without left ventricular dilatation (left ventricular end-diastolic dimension 53 mm). In spite of intensive treatment, her biventricular heart failure progressed, and a second echocardiography showed depressed systolic mitral annular excursion, right ventricular dilatation and systolic dysfunction, granular high-intensity echo-speckles in the interventricular septum, and restrictive pattern of the transmitral Doppler indices. These echocardiographic findings correspond to cardiac hemochromatosis. Here we report this case of cardiac hemochromatosis diagnosed by echocardiography.

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We present three rare cases of fetal cardiac tumor. Case 1: A 30-year-old multipara was referred to our hospital at 38 weeks pregnant. Fetal ultrasonographic examination revealed a homogeneous, hyperechogenic tumor in the left ventricle (13 mm in diameter). A part of the tumor protruded into the ascending aorta. A male neonate (gestational age 39 weeks and 1 day, weight 3,966 g) was born via vaginal delivery. Tumor resection was performed at the age of 1 day, and the histopathological diagnosis was rhabdomyoma. Brain MRI confirmed tuberous sclerosis at the age of two and a half months. He had epilepsy. The tumor has not recurred as of age 5 years. Case 2: A 30-year-old multipara was referred to our hospital at 29 weeks and 5 days pregnant because of three homogeneous, hyperechogenic tumors in the fetal left ventricle, right ventricle, and right atrium (14 mm, 17 mm, and 5 mm in diameter, respectively). A female neonate (gestational age 39 weeks and 5 days, weight 2,866 g) was born via vaginal delivery. She was diagnosed with tuberous sclerosis by brain CT at the age of 3 days. She had epilepsy. The sizes of the tumors have not changed as of age 3 years. Case 3: A 36-year-old primipara was referred to our hospital at 19 weeks and 5 days pregnant because of a homogeneous, hyperechogenic tumor in the fetal left ventricle (10 mm in diameter). A female neonate (gestational age 37 weeks 4 days, weight 3,006 g) was born via vaginal delivery. Ventricular tachycardia appeared at the age of 13 days. The size of the tumor has not changed as of age 9 months. Factors for poor prognosis of fetal cardiac tumor include tumor size of 20 mm or larger, fetal arrhythmia, and hydrops fetalis. This study contributes to the further investigation of prognostic factors.

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