本研究グループでは，秒間数千枚を達成する超高速超音波イメージングによる組織動態計測に関する研究を行っている．動態計測のためには，受信超音波信号から対象物の変位を推定する必要がある．しかし一般的には，受信超音波信号は伝搬方向に比べその垂直(横)方向の周波数が低いため，横方向の変位推定精度が低い．横方向の超音波音場の変動周波数を向上させる手法として，横方向変調法がある．横方向変調法は，受信遅延和ビームフォーミング時のアポダイゼーションにより実現できる．一方，方位分解能を向上させる手法として，適応ビームフォーミングがある．しかし適応ビームフォーミングでは通常アポダイゼーションは用いておらず，横方向変調には用いることができない．本研究では，適応ビームフォーマにアポダイゼーションを導入し，横方向変調への適用を試みた．超音波画像評価用ファントムを用いて基礎実験を行ったところ，従来の遅延和ビームフォーミングによる横方向変調に比べ，適応ビームフォーミングを用いた場合にはより急峻な横方向の変調を実現できた． Jensen JA. A new method for estimation of velocity vectors. IEEE Trans. Ultrason.Ferroelectr. Freq. Control 1998;45:837-851.
音響化学療法は集束超音波と色素系薬剤の腫瘍集積性を利用したダブルターゲティングがん治療法として注目されている．しかしながら，抗腫瘍効果の作用機序は明確になっていない．我々は音響化学療法における抗腫瘍効果の作用機序がキャビテーションによって生成されるヒドロキシラジカルなどのラジカル種から色素増感剤への電子移動によって生成される色素由来のラジカル種によると仮定した．色素由来の炭素センターラジカルはヒドロキシラジカルと比較して長寿命であることから，細胞膜の酸化反応を高効率で誘発することが予想される．本発表ではラジカル反応開始剤であるAAPHを用いてヒドロキシラジカルを生成し，それの抗腫瘍効果が光線力学療法及び音響力学療法で広く用いられているchlorin e6（Ce6）色素によって増大されたことについて報告する．培養細胞を用いた検討において100 mM AAPHの抗腫瘍効果がCe6存在下で20倍程度増大した．一方で，光線力学療法の色素として知られているテトラスルホン酸フタロシアニン（電子的安定）はAAPHの抗腫瘍効果を増大させなかった．今後，超音波照射による抗腫瘍効果が同様な傾向であるか検討を行う．
Risk factors for aneurysm rupture have been studied extensively in the past, with several factors showing significant correlations with rupture status. We analysed seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Patient data (age and sex), morphometric factors (aneurysm maximum height and volume, aspect ratio, bifurcation angle, bottleneck ratio, and neck-parent artery ratio) and hemodynamic factors (inflow coefficient and wall shear stress) were compared between ruptured and unruptured groups, and statistically analyzed. Aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with the rupture status on univariate analysis. Logistic regression analysis showed that aspect ratio and bifurcation angle were predictors of rupture. Bifurcation angle correlated inversely with inflow coefficient which in turn correlated directly with wall shear stress on Pearson’s correlation coefficient Bifurcation angle and aspect ratio were independent predictors for aneurysm rupture.
A methodology allowing a combined analysis of pathological human thoracic aorta (TA) using both 4D flow MRI and computational fluid dynamics (CFD) is presented. MR images from patient with aneurysm have been acquired with a 4D Flow MRI sequence. The segmentation of the aorta has been performed on the PCMRA image. A volumetric tetrahedral mesh with one inlet and four outlets was generated. In CFD simulations, blood density and viscosity were assumed to be 1060kg/m3 and 4.10-3 Pa.s, respectively. MRI velocity measurements have been used as boundary conditions. CFD simulations have been compared to MRI measurements both qualitatively and quantitatively. A visual evaluation using streamlines and volumetric flow rates at the outlets show good agreements. Moreover, hemodynamics parameters such as WSS have been computed and allow for the evaluation of stress areas. A methodology for a combined analysis of TA taking advantage of both MRI and CFD was proposed.
In the present study, the author constructed an EC-SMC co-culture model with SMCs 3D cultured in a collagen gel, and SMCs phenotype was controlled into a contractile state. Then, different magnitudes of shear stress (SS) were applied to the co-culture model and the results showed that a high SS of 10 Pa could induce higher matrix metalloproteinases (MMPs) productions from SMC in the co-culture model. As to understand ECs influence on SMC responses, TGF-β1 (Transforming growth factor beta 1) expression from ECs were suppressed by an SiRNA transfection method in the present study. Compared to different MMP-2 production levels under different SS in the normal co-culture model, SMCs showed same MMP-2 production level under all SS conditions in the co-culture model with transfected ECs. This result means that TGF-β1 expression from ECs could influence SMCs response to SS in a co-culture model.
Restenosis is known as common problem during stent treatment. Stent optimization has been introduced to find the best design criteria in order to improve the endovascular treatment efficacy. Surrogate method is known as efficient method of optimization that has been built up from finite element method (FEM) simulation. Besides obtaining the optimized criteria, response surface plot which constructed by Kriging surrogate estimation process is also beneficial to study the behavior of design variables towards objective functions. In this study, we constructed the response surface map from stent design parameter configuration of strut size and inter-strut gap towards objective function. Our objective function is to minimizing the percentage of low wall shear stress area along deployment region. With this response surface, broad analysis on the stent performance can be clearly observed. More recommendations on how combinations between stent strut’s size and gap should be designed are successfully obtained by this study.
Endovascular devices are medical devices inserted into the arteries in case of aneurysm. This minimally invasive treatment is preferred in case of aged patient. The number of commercially available device designs increased on the market but no data exist regarding direct comparisons of their performance, difficult to perform in vivo. The purpose of this research is to create in vitro experimental platforms allowing the study of the influence of those medical devices by monitoring the hemodynamic changes occurred during their deployments. Precise multi-scale evaluation of pressure and flow rate into the arteries surrounding the aneurysm are performed and synchronized to each step of the medical procedure. Further analysis are also conducted on the geometry of the deployed devices and flow pattern changes after deployment. As a proof of concept, studies of the treatment of an abdominal aortic aneurysm and an intracranial aneurysm are presented.
Ultrasonic cavitation is of great interest in various biomedical applications. In cancer therapy, various ways to enhance chemotherapeutic agents has been explored. The present work emploies a two confocal transducers apparatus and a control loop with passive cavitation detector to generate cavitation in a controlled manner. Firstly, in vitro experiments show for stable cavitation the possibility to increase the efficacy of doxorubicin. Mechanistic studies suggest an indirect interaction between cavitation and the efficiency of DNA repair processes of the studied 4T1 tumor cells. Although this result was not observable in vivo, a safety study was conducted in vivo. Both the effect on healthy tissues and the potential metastatic spreading were assessed. Only slight damages were observed on healthy tissues. It was also shown a reduced metastatic spreading compared in mice which received ultrasound. This suggests the safety and the possibility to employ cavitation in vivo.
"In this study we characterize the mechanical behavior of human skin on its surface and volume, following an impact induced wave propagation. Spatial and temporal speed of the induced wave propagation are our physical criteria correlated to the skin rheological character. This study comports two main aspects of measurement on the forearm area: 1)The first aspect is the exploitation of the surface wave propagation induced by air blast impact to evaluate its viscoelastic mechanical behavior of the skin. 2)The second aspect is the use of the 20 MHz ultrasonic echography as monitoring tool, to follow the wave propagation in the skin volume and evaluate of the mechanical properties gradient. In order to validate the developed approaches, measurements have been realized on healthy volunteers representing age and gender effect. The obtained results confirm the efficiency of the developed instrumentation to evaluate the skin viscoelastic properties on surface and volume."
We developed both a non-contact urination measuring system as a toilet sheet shape and a cloud network system to store and to utilize the urination data for diagnosis or nursing care. The measuring system consists of a non-contact thermal sensor, a vibration sensor, and wireless communication. Urination is measured by the non-contact thermal sensor. Personal identification is achieved by walking vibration. These data are transmitted via Wi-Fi and a mobile virtual network operator, and are stored in one database. The urination data is displayed on a tablet PC. This study was partly supported by SCOPE (162305003), Minister for Internal Affairs and Communications.
再生医療では、移植医療に必要な重要臓器の作製が求められている。そのためには、複雑かつ立体構造を持つ組織を迅速に作製する技術が必要である。そこで我々は、3次元積層造形した後プレ培養した組織パーツを作製し、それらを組み立てるバイオアセンブリのアプローチを目指している。これまで、細胞を配置した3次元積層造形を可能にする3D Bio printerを開発し、また、造形性と細胞接着性に優れたバイオインク材料の開発を行い、優れたゲル材料を見出してきた。さらに、血管内皮細胞との親和性の高いゲル材料の開発を行い、血管内皮細胞の伸展を確認している。そこで、今回心筋細胞を播種または包埋した3次元組織パーツ構造をデザインして構築しプレ培養を行い、心筋組織パーツとしての機能を評価した。実験方法として、自前で開発した3D Bio printerを用いて、造形性と細胞接着性に優れたゲル材料で3次元構造物を作製し、心筋細胞を直接播種して培養を行った。組織学的評価として細胞の配向を観察し、生理学的評価として、Caイメージングとアドレナリン負荷試験を行った。 その結果、自発的に拍動する3次元構造物の作製に成功した。組織学的評価で細胞の配向性を確認し、アドレナリン負荷試験で拍動数の増加を認めた。これからは血管内皮細胞に親和性の高いゲル材料と血管内皮細胞を加えての共培養、作製した心筋組織パーツのアセンブリにチャレンジしたい。