Naotaka Nitta

Long-term results of cell-free biodegradable scaffolds for in situ tissue-engineering vasculature: in a canine inferior vena cava model.

We have developed a new biodegradable scaffold that does not require any cell seeding to create an in-situ tissue-engineering vasculature (iTEV). Animal experiments were conducted to test its characteristics and long-term efficacy. An 8-mm tubular biodegradable scaffold, consisting of polyglycolide knitted fibers and an L-lactide and ε-caprolactone copolymer sponge with outer glycolide and ε-caprolactone copolymer monofilament reinforcement, was implanted into the inferior vena cava (IVC) of 13 canines. All the animals remained alive without any major complications until euthanasia. The utility of the iTEV was evaluated from 1 to 24 months postoperatively. The elastic modulus of the iTEV determined by an intravascular ultrasound imaging system was about 90% of the native IVC after 1 month. Angiography of the iTEV after 2 years showed a well-formed vasculature without marked stenosis or thrombosis with a mean pressure gradient of 0.51±0.19 mmHg. The length of the iTEV at 2 years had increased by 0.48±0.15 cm compared with the length of the original scaffold (2–3 cm). Histological examinations revealed a well-formed vessel-like vasculature without calcification. Biochemical analyses showed no significant differences in the hydroxyproline, elastin, and calcium contents compared with the native IVC. We concluded that the findings shown above provide direct evidence that the new scaffold can be useful for cell-free tissue-engineering of vasculature. The long-term results revealed that the iTEV was of good quality and had adapted its shape to the needs of the living body. Therefore, this scaffold would be applicable for pediatric cardiovascular surgery involving biocompatible materials.

Estimation of Nonlinear Elasticity Parameter of Tissues by Ultrasound

In this paper, a new parameter that quantifies the intensity of tissue nonlinear elasticity is introduced as the nonlinear elasticity parameter. This parameter is defined based on the empirical information that the nonlinear elastic behavior of soft tissues exhibits an exponential character. To visualize the quantitative nonlinear elasticity parameter, an ultrasonic imaging procedure involving the three-dimensional finite element method (3-D FEM) is presented. Experimental investigations that visualize the nonlinear elasticity parameter distribution of a chicken gizzard and a pig kidney embedded in a gelatin-based phantom were performed. The values extracted by ultrasound and 3-D FEM were compared with those measured by the direct mechanical compression test. Experimental results revealed that the nonlinear elasticity parameter values extracted by ultrasound and 3-D FEM exhibited good agreement with those measured by the mechanical compression test, and that the intensity of tissue nonlinear elasticity could be visualized quantitatively by the defined nonlinear elasticity parameter.

Real-Time Three-Dimensional Velocity Vector Measurement using the Weighted Phase Gradient Method

Although the technique for measuring blood flow based on the ultrasonic Doppler method is an important means for clinical diagnosis, it is inappropriate for quantitative assessment of blood flow since the true three-dimensional (3-D) velocity component cannot be obtained in many cases. In this paper, to overcome the restriction, a new method of 3-D velocity vector measurement is proposed. By detecting the gradient of the weighted phase shift distribution on the receiving aperture, the proposed method enables us to employ a smaller single aperture compared with those used in conventional techniques, and its sensitivity is independent of the direction of transverse flow. Furthermore, real-time measurement can be realized since the autocorrelation technique is utilized for the phase shift extraction as well as the present Doppler method. The basic performance of the method is evaluated by computer simulation. Moreover, sector scan imaging is constructed by the proposed method and compared with the conventional method. The obtained results validated the feasibility and ability of the proposed method for measuring 3-D velocity.

A Method of Tissue Elasticity Estimation Based on Three-Dimensional Displacement Vector

For assessing the tissue elastic properties based on 3D information of displacement and strain induced by static deformation, we propose an estimator of 3D displacement vectors. This method is composed of the combination of the weighted phase gradient method (WPG), which utilizes the gradient of the plane obtained from the phase shift at each receiving element on the 2D array, and combined autocorrelation method (CA), which is phase domain processing without aliasing. Large displacements required for highly accurate measurements can be measured by this method. In addition, we develop a tissue elasticity reconstruction method using the measured 3D displacement vectors. Computer simulations reveal that our methods are valid for evaluating the elastic structures of tissues based on 3D information.

Experimental Investigation of 3-D Blood Flow Velocity Measurement.

Ultrasonic pulse Doppler tomography is generally applied to noninvasive vascular measurement. The present method, however, measures only one component along the beam direction of a three-dimensional (3-D) velocity vector and provides useful information only if the beam direction in relation to the flow velocity vector is known. Images obtained by such systems are not only unsuitable for quantitative evaluation and but also prone to misinterpretation. On the other hand, in terms of real-time data acquisition achieved by scanning 3-D space, a two-dimensional (2-D) array probe is expected to become indispensable for future clinical applications. From this point of view, we have proposed a method of measuring a 3-D velocity vector using the 2-D array probe. In this paper, the principles of the proposed approach are introduced and experimental data obtained using a prototype system and the flow phantom are processed. Experimental results validate the usefulness of the method and its potential for practical use.

Ultrasonic Measurement of Fluid Viscosity for Blood Characterization

Although plaque rupture in arteriosclerosis is affected by not only its strength but also by hemodynamic factors, such as blood pressure and shear stress, in particular, the viscous coefficient which directly controls the magnitude of shear stress might be a risk factor in plaque rupture. Therefore, if the viscous coefficient can be assessed noninvasively, it can be a useful index for prediction of a plaque rupture and assessment of various diseases. In this work, an ultrasonic methodology to estimate the viscous coefficient was investigated by numerical simulation and flow-phantom experiment as the fundamental investigation for noninvasively assessing the viscous characteristics of blood. These results show that the proposed method is useful for estimating the kinematic viscosity coefficient in the viscous evaluation of blood.

Assessment of vulnerable coronary plaque by intravascular elasticity imaging

Plaque rupture is regarded as one of the main causes of acute coronary syndromes. To prevent plaque rupture and guide a pharmacological treatment, it is important to image the weak (fragile) part of atherosclerotic plaque. Our preliminary experiments revealed the feasibility of a strain image using IVUS (intravascular ultrasound) to discriminate between different types of plaque. For the purpose of obtaining finer and more stable assessments of vulnerable plaque under interventional conditions, we propose a strain power image as an index of tissue deformability by analyzing the time-varying strain profiles obtained from the IVUS data. We also conducted an in vivo test with a new acquisition device that allows us to capture a large scale of RF data. The results demonstrate that strain power imaging has the potential to evaluate the vulnerability of plaques.

Experimental system for in-situ measurement of temperature rise in animal tissue under exposure to acoustic radiation force impulse

PurposeAcoustic radiation force impulse (ARFI) has recently been used for tissue elasticity measurement and imaging. On the other hand, it is predicted that a rise in temperature occurs. In-situ measurement of temperature rise in animal experiments is important, yet measurement using thermocouples has some problems such as position mismatch of the temperature measuring junction of the thermocouple and the focal point of ultrasound. Therefore, an in-situ measurement system for solving the above problems was developed in this study.MethodsThe developed system is composed mainly of an ultrasound irradiation unit including a custom-made focused transducer with a through hole for inserting a thin-wire thermocouple, and a temperature measurement unit including the thermocouple.ResultsThe feasibility of the developed system was evaluated by means of experiments using a tissue-mimicking material (TMM), a TMM containing a bone model or a chicken bone, and an extracted porcine liver. The similarity between the experimental results and the results of simulation using a finite element method (FEM) implied the reasonableness of in-situ temperature rise measured by the developed system.ConclusionThe developed system will become a useful tool for measuring in-situ temperature rise in animal experiments and obtaining findings with respect to the relationship between ultrasound irradiation conditions and in-situ temperature rise.

Non-invasive speed of sound measurement in cartilage by use of combined magnetic resonance imaging and ultrasound: an initial study

The speed of sound (SOS) is available as an index of elasticity. Using a combination of magnetic resonance imaging (MRI) and ultrasound, one can measure the SOS. In this study, we verified the accuracy of SOS measurements by using a combination of MRI and ultrasound. The accuracy of the thickness measurements was confirmed by comparison of the results obtained with use of MRI with those of a non-contact laser, and the accuracy of the calculated SOS values was confirmed by comparison of the results of the combined method and ultrasound measurements with the transmission method ex vivo. There was no significant difference between thickness measurements by MRI and those with the non-contact laser, and there was a significant linear correlation between SOS measurement results by use of the combined method and those by use of the transmission method. We also showed that the SOS values obtained agreed with those of previously published studies.

Magnetic resonance elastography using an air ball-actuator

The purpose of this study was to develop a new technique for a powerful compact MR elastography (MRE) actuator based on a pneumatic ball-vibrator. This is a compact actuator that generates powerful centrifugal force vibrations via high speed revolutions of an internal ball using compressed air. This equipment is easy to handle due to its simple principles and structure. Vibration frequency and centrifugal force are freely adjustable via air pressure changes (air flow volume), and replacement of the internal ball. In order to achieve MRI compatibility, all parts were constructed from non-ferromagnetic materials. Vibration amplitudes (displacements) were measured optically by a laser displacement sensor. From a bench test of displacement, even though the vibration frequency increased, the amount of displacement did not decrease. An essential step in MRE is the generation of mechanical waves within tissue via an actuator, and MRE sequences are synchronized to several phase offsets of vibration. In this system, the phase offset was detected by a four-channel optical-fiber sensor, and it was used as an MRI trigger signal. In an agarose gel phantom experiment, this actuator was used to make an MR elastogram. This study shows that the use of a ball actuator for MRE is feasible.