Ryo Nagaoka

High-Resolution Ultrasound Imaging of Human Skin In Vivo by Using Three-Dimensional Ultrasound Microscopy

Observing the morphology of human skin is important in the diagnosis of skin cancer and inflammation and in the assessment of skin aging. High-frequency ultrasound imaging provides high spatial resolution of the deep layers of the skin, which cannot be visualized by optical methods. The objectives of the present study were to develop a three-dimensional (3-D) ultrasound microscope and to observe the morphology of normal human skin in vivo. A concave polyvinylidene fluoride transducer with a central frequency of 120 MHz was excited using an electric pulse generated by semiconductor switching. The transducer was scanned two-dimensionally by using two linear motors on the region-of-interest and the ultrasonic reflection was digitized with 2-GHz sampling. Consecutive B-mode images perpendicular to the skin surface were reconstructed to generate multiplanar reconstructed images and 3-D volume-rendering images clearly showing microstructures such as sebaceous glands and hair follicles. The 3-D ultrasound microscope could be used to successfully image the morphology of human skin noninvasively and may provide important information on skin structure.

Basic study of intrinsic elastography: Relationship between tissue stiffness and propagation velocity of deformation induced by pulsatile flow

We proposed an estimation method for a tissue stiffness from deformations induced by arterial pulsation, and named this proposed method intrinsic elastography (IE). In IE, assuming that the velocity of the deformation propagation in tissues is closely related to the stiffness, the propagation velocity (PV) was estimated by spatial compound ultrasound imaging with a high temporal resolution of 1 ms. However, the relationship between tissue stiffness and PV has not been revealed yet. In this study, the PV of the deformation induced by the pulsatile pump was measured by IE in three different poly(vinyl alcohol) (PVA) phantoms of different stiffnesses. The measured PV was compared with the shear wave velocity (SWV) measured by shear wave imaging (SWI). The measured PV has trends similar to the measured SWV. These results obtained by IE in a healthy male show the possibility that the mechanical properties of living tissues could be evaluated by IE.

Measurement of regional pulse-wave velocity using spatial compound imaging of the common carotid artery in vivo.

Pulse-wave velocity (PWV) is an important index for diagnosing cardiovascular diseases. The pulse wave is volumetric change induced by heartbeat or inflowing blood, and significantly depends on the propagating path and stiffness of the artery. In this study, PWV of the propagating wave was visualized using spatial compound imaging with high temporal resolution. The frame rate was 1000 Hz, or a time interval of 1 ms. Subjects were four young healthy males and one young healthy female (n=5, age: 23.8±1.17 years old), and the measurement area was the right common carotid artery. PWVs in four phases (the four phases of heart valve opening and closing) were investigated during a cardiac cycle. In phase I, the heart pulsates. In phase II, the tricuspid and mitral valves close, and the aortic and pulmonic valves open. In phase III, the tricuspid and mitral valves open, and the aortic and pulmonic valves close. In phase IV, the propagating wave is reflected. PWVs in phases II and III were easily observed. PWVs were 3.52±1.11 m/s in phase I, 5.62±0.30 m/s in phase II, 7.94±0.85 m/s in phase III, and -4.60±0.99 m/s for the reflective wave. PWV was measured using Spatial Compound Imaging with high temporal resolution, and the PWV in each phase may be used as the index for diagnosing stages of arteriosclerosis progression.

Ultrasonic Measurement of Microdisplacement Induced by Acoustic Radiation Force

Quantitative evaluation of human skin aging is achieved by measuring the viscoelasticity of the skin. In the present study, microdisplacement induced by acoustic radiation force (ARF) is quantitatively measured by high-frequency ultrasonography (HFUS) and the result is confirmed by laser-Doppler velocimetry (LDV). Poly(vinyl alcohol) (PVA) with 1% cellulose particles was used as the biological phantom. A concave piezoelectric zirconate titanate (PZT) transducer with a diameter and focal length of 3 cm was used as an applicator to generate ARF. Microdisplacement at each depth of PVA was measured by the phased tracking method at 100 MHz of ultrasound with a repetition rate of 2000 Hz. When 80 tone-burst pulses were applied, the displacement measured by HFUS was 9 µm and the same result was obtained by LDV. As the displacement at each depth of PVA is measurable using ARF and the HFUS system, the system could be applied to measuring the viscoelasticity of the layered structure of the human skin.

Imaging of sebaceous glands of human skin by three-dimensional ultrasound microscopy and its relation to elasticity

High frequency ultrasound imaging has realized high resolution in vivo imaging of the biological tissues at a microscopic level. Human skin structure, especially sebaceous glands at the deep part of the dermis, was observed by three-dimensional ultrasound microscopy with the central frequency of 120 MHz. The visco-elasticity and surface sebum level of the observed region were measured by established testing devices. Both sebaceous glands density and surface sebum level were higher in cheek than those in forearm. The viscosity of forearm was lower than that of cheek. These results suggest that sebaceous glands may act as cushions of the skin besides their classical role of secreting sebum and some hormones. High frequency ultrasound imaging contributes to the evaluation of human skin aging.

Development of Real-Time 3-D Photoacoustic Imaging System Employing Spherically Curved Array Transducer

Photoacoustic (PA) imaging is a promising imaging modality to visualize specific living tissues based on the light absorption coefficients without dyeing. In this paper, a real-time PA imaging system with a tunable laser was newly developed with an originally designed spherically curved array transducer. Five different series of experiments were conducted to validate the PA measurement system. The peak frequency of the transducer response was 17.7 MHz, and a volume-imaging rate of 3-D volume imaging was 10–20 volumes per second. The spatial resolution of imaging was 90–

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

105~\mu \text{m}

A method for the design of ultrasonic devices for scanning acoustic microscopy using impulsive signals

along both the axial and lateral directions. The developed imaging system could measure a difference on an absorption coefficient of gold nanorods. Additionally, the PA imaging could visualize the in vivo microvasculatures of a human hand. This PA imaging system with higher spatial–temporal resolution and the tunable laser further should enhance our understanding of not only basic properties of the photo acoustics but also clinical applications.

Visualization of murine lymph vessels using photoacoustic imaging with contrast agents

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.

Visualization of the microcirculation in micro vasculatures by photoacoustic tomography with high frequency spherical array transducer

HighlightsA new plane‐wave model to calculate loss of ultrasonic devices was developed.Two point‐focus‐beam ultrasonic devices with a ZnO transducer were fabricated.The frequencies at which the losses of devices became minimum corresponded to the calculated values. ABSTRACT Scanning acoustic microscopy (SAM) using impulsive signals is useful for characterization of biological tissues and cells. The operating center frequency of an ultrasonic device strongly depends on the performance characteristics of the device if the measurement is conducted by using impulsive signals. In this paper, a method for the design of ultrasonic devices for SAM using impulsive signals was developed. A new plane‐wave model was introduced to calculate frequency characteristics of loss of ultrasonic devices by taking into account the conversion loss at the ultrasonic transducer, the transmission loss at the acoustic anti‐reflection coating, and the propagation loss in the couplant. Ultrasonic devices were fabricated with a ZnO ultrasonic transducer using two acoustic lenses with aperture radii of 1.0 mm and 0.5 mm, respectively. The frequencies at which measured losses became minima corresponded to the calculation results by the plane‐wave model. This numerical calculation method is useful for designing ultrasonic devices for acoustic microscopy using impulsive signals.