山口 匡

To understand physiologic state in diseased liver e.g. non-alcoholic steatohepatitis, this study aims to analyze the acoustic impedance (Z) of hepatic cells using a scanning acoustic microscopy (SAM). Ultrasound scattering sources in cells, however, cause the multi-reflection and prevent from analyzing the precious value of Z although it provides the useful information of structure in cells (M. N. Fadhel et al. 2015). A similar effect also occurs in case of a part of cells apart from substrate. As the fundamental study, this study discusses the effect of multi-reflection on the analysis of the Z of cultured cells.

皮膚潰瘍の治癒状況や感染発症の有無を非侵襲かつ定量的に診断する手法が求められている。新規診断法の可能性として、超音波による組織性状診断技術の応用を検討しており、その定量診断技術の基礎となる信号解析法を検討した。信号解析法として生体組織の散乱特性を考慮した統計分布を用い、エコー信号の振幅分布を数学モデル化することで、皮膚潰瘍からのエコー信号の散乱特性を評価した。さらに、組織病理学的評価により組織の空間的特徴を観察し、主に非感染および感染組織の構造に着目した。動物実験について、臨床用の超音波診断装置と中心周波数8.9MHZのリニアアレイプロープを用いて、皮膚潰瘍を有する3種のラットモデル(非感染・表層感染・深層感染モデル)からのRFエコー信号を取得した。まず、実測と推定された統計分布間の一致度を評価することで、数学モデル化精度の高い統計分布を確認した。さらに、数学モデル化精度の高い統計分布のパラメータを用いて、非感染および感染組織の差を指標化した。結果、感染をモデル化したラットにおいてのみ、干渉信号のパワーに関係する統計分布のパラメータが感度を示し、そのパラメータの空間分布の特徴は、対応する断面の組織病理像の特徴と一致した。(著者抄録)

A two-dimensional (2D) computational model of acoustic impedance constructed from histological tissue images, termed 2D impedance map (2DZM), was recently proposed to obtain quantitative information about tissue scattering (Luchies & Oelze 2016). However, this 2DZM approach was limited to isotropic and sparse media. The present study investigates the 2D structure factor model (SFM) in 2DZM approaches to take into account coherent scattering occurring in dense media. Studies of simulated 2DZMs were performed to evaluate the ability of 2D SFM-based approach to accurately quantify scattering. Polydisperse spheres with a gamma radius distribution were uniformly randomly distributed in a 3D volume to mimic a collection of whole cells. 2DZMs were obtained from simulated 3D media by performing perfect cross sections. The 2D backscatter coefficient (BSC) was computed by averaging the magnitude squared of the 2D Fourier transforms of 50 extracted 2D relative impedance contrast maps. The 2D BSC was fit to three theoretical models over the 1-100 MHz frequency range. A sparse fluid disc model (FDM) and a concentrated structure factor model (SFM) were compared to estimate the mean scatterer size and acoustic concentration for scatterer volume fractions ranging from 0.6% to 30%. In the case of the SFM, both monodisperse and polydisperse models were studied. Results demonstrated that the polydisperse SFM fitted satisfactorily the simulated BSCs of sparse and dense media. Scatterer radius and surface fraction estimates demonstrate the superiority of the 2D SFM-based approach over a wide range of studied volume fractions. Relative errors were less than 4% for the scatterer radius estimates and less than 10% for the surface fraction estimates when using the concentrated model (against 35% and 50%, respectively, when using the sparse model). The results establish the ability of the 2D SFM-based approach to accurately estimate scatterer properties from 2DZMs even in the challenging case of dense media.

Giant cluster-like vesicles (GCVs) encapsulating near-infrared fluorescent liposomes and X-ray contrast agents coated with lipids can play a multifunctional role, e.g. preoperatively and intraoperatively localizing tumors and reservoir of a fluorescent tracer for detecting sentinel lymph nodes if they are destroyed. We propose the method to assess the destruction of GCVs using the interaction between the ultrasound (US) and ultrasound contrast agents (UCAs). The GCVs were exposed to 2.8 MHz ultrasound with commercial UCA solution. The negative peak pressure of ultrasound was 0, 0.06, 0.56, 1.1 and 1.6 MPa. The measurements of radii of GCVs was conducted after ultrasound exposure. The result demonstrated that bigger GCVs are split to become many smaller GVs. The results indicated that the interaction between US and UCA enhances the destruction of bigger GCVs and increased the amount of smaller GCVs.

Non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) can be achieved by quantitative ultrasound (QUS), which requires a detailed understanding tissue-specific acoustic microstructure at cellular scale (i,e., 10 mu m). This study focuses on obtaining speed of sound (c) of organelles (i.e., nucleus, cytoplasm, and fibers) using 250-MHz ultrasound in rat livers. Three different pathological stages were investigated in rat models: normal (control: n = 2), NASH (n = 3), and fibrosis model (n = 6). After animal sacrifice, each liver was fixed in formalin and a 7-mu m thin section was affixed to glass slide using a microtome. A scanning acoustic microscopy system equipped with a 250-MHz center-frequency transducer was employed to obtain two-dimensional (2D) maps of c with a spatial resolution of 7-mu m. The histological images were used to detect the positions of the nuclei, cytoplasm and fibers, and the corresponding c values from obtained from the co-registered 2D c map. For all organelles, Kruskal-Wallis test reveals a significant difference (p < 0.01) between all paired stages. These results reveals that c is the highest in fibrosis livers for all organelles. Additionally, in NASH livers, c of nuclei and cytoplasm were the lowest, which could be due to intracellular fluid or ballooning of the whole cell. As expected, c in fiber changes with pathologic state. Results reveal that c of the nucleus and cytoplasm also changes with pathologic state and that we were able to carefully assess these differences using 250-MHz ultrasound. These results could prove invaluable to improve in vivo QUS investigations of livers.

<p>Phantoms for ultrasonography have been widely used to improve skills of physicians and techniques of ultrasonic scattering. Several kinds of phantoms for ultrasonography have already been developed using gelatin, Polyacrylamide. In the development of biomodel for ultrasonography that covers human soft tissue, to change the mechanical properties widely is useful. We chose a poly (vinyl alcohol) hydrogel (PVA-H) to mimic human soft tissue. The purpose of this study is to measure the mechanical properties with varieties of concentration of solvent of PVA solution. The ratio of the mixed solution of Dimethyl sulfoxide (DMSO) and water was changed. The measurement of the static viscoelasticity, the dynamic viscoelasticity, and the loss tangent of PVA-H were performed. In addition, we measured the transverse wave velocity for the phantom to which graphite was added. In conclusion, the variety of mechanical properties of PVA-H is shown by the change of solvents, and especially the loss tangent is twice higher than the conventional PVA-H. And the transverse wave velocity has also a relation to the solvents.</p>

超音波による組織性状の定量診断技術が近年盛んに開発されているが，より高精度な診断のためには各種の生体組織が有する固有の音響特性と病理学的性質との詳細な関係性についての理解が必要不可欠である．本研究では，音波伝搬に関わるパラメータである音響インピーダンスと音速に着目し，病態の異なる4種類のラット肝臓（正常・脂肪肝・非アルコール性脂肪性肝炎（NASH）・硬変肝）について、中心周波数が80 MHzの振動子を搭載した超音波顕微鏡を用いて組織学的微細構造との関係を検討した．病理写真との比較により脂肪肝およびNASHでは脂肪滴が多数認められ，音響インピーダンスおよび音速はどちらも正常肝と比較してわずかではあるが統計的に低値，線維肝は高値となった（&lt;i&gt;p&lt;/i&gt;&lt;0.01）．この結果は，肝臓内に脂肪および線維が沈着することによる組織変性を反映していると考えられる．以上より，肝組織の変性状態を音響特性を指標として判定できる可能性が示唆された．