High-Frequency Acoustic Impedance Imaging of Cancer Cells

Variations in the acoustic impedance throughout cells and tissue can be used to gain insight into cellular microstructures and the physiologic state of the cell. Ultrasound imaging can be used to create a map of the acoustic impedance, on which fluctuations can be used to help identify the dominant ultrasound scattering source in cells, providing information for ultrasound tissue characterization. The physiologic state of a cell can be inferred from the average acoustic impedance values, as many cellular physiologic changes are linked to an alteration in their mechanical properties. A recently proposed method, acoustic impedance imaging, has been used to measure the acoustic impedance maps of biological tissues, but the method has not been used to characterize individual cells. Using this method to image cells can result in more precise acoustic impedance maps of cells than obtained previously using time-resolved acoustic microscopy. We employed an acoustic microscope using a transducer with a center frequency of 375 MHz to calculate the acoustic impedance of normal (MCF-10 A) and cancerous (MCF-7) breast cells. The generated acoustic impedance maps and simulations suggest that the position of the nucleus with respect to the polystyrene substrate may have an effect on the measured acoustic impedance value of the cell. Fluorescence microscopy and confocal microscopy were used to correlate acoustic impedance images with the position of the nucleus within the cell. The average acoustic impedance statistically differed between normal and cancerous breast cells (1.636 ± 0.010 MRayl vs. 1.612 ± 0.006 MRayl), indicating that acoustic impedance could be used to differentiate between normal and cancerous cells.     

Value of Acoustic Radiation Force Impulse Imaging Elastography for Non-invasive Evaluation of Patients with Nonalcoholic Fatty Liver Disease

The goals of the work described here were to evaluate the clinical utility of acoustic radiation force impulse (ARFI) elastography in differentiating non-alcoholic fatty liver disease (NAFLD) histologic subtypes and to determine if ARFI elastography measurements correlate with the severity of liver fibrosis. We compared ARFI elastography measurements with clinical, biologic and histologic features (simple steatosis or steatohepatitis) in 64 patients with histologically proven NAFLD. ARFI elastography is suitable for distinguishing patients with non-alcoholic steatohepatitis from those with simple steatosis, with an area under the receiver operating characteristic curve (AUROC) of 0.867 (95% confidence interval = 0.782–0.953). There was a highly significant correlation (r = 0.843) between ARFI elastography measurements and fibrosis (p < 0.001). In patients with non-alcoholic steatohepatitis, the diagnostic performance of ARFI elastography in predicting significant fibrosis (F ≥ 2) had an AUROC of 0.944. ARFI elastography better predicted F = 4 fibrosis (AUROC = 0.984). In conclusion, ARFI elastography is a promising method for differentiating patients with non-alcoholic steatohepatitis from patients with simple steatosis and can also predict significant fibrosis in these patients.     

Evaluation of Non-alcoholic Fatty Liver Disease Using Acoustic Radiation Force Impulse Imaging Elastography in Rat Models

The aim of this study is to evaluate the utility of acoustic radiation force impulse (ARFI) elastography for assessing hepatic fibrosis stage and non-alcoholic fatty liver disease (NAFLD) severity, as well as the relationship among hepatic histologic changes using shear wave velocity (SWV). Animal models with various degrees of NAFLD were established in 110 rats. The right liver lobe was processed and embedded in a fabricated gelatin solution (porcine skin). Liver mechanics were measured using SWV induced by acoustic radiation force. Among the histologic findings, liver elasticity could be used to differentiate normal rats from rats with simple steatosis (SS) as well as distinguish SS from non-alcoholic steatohepatitis (NASH), with areas under the receiver operating characteristic curves (AUROC) of 0.963 (95% confidence interval = 0.871–0.973) and 0.882 (95% confidence interval = 0.807–0.956), respectively. For NAFLD rats, the diagnostic performance of ARFI elastography in predicting significant fibrosis (F ≥ 2) had an AUROC of 0.963. For evaluating steatosis severity, we found a progressive increase in ARFI velocity proportional to steatotic severity in NAFLD rat models, but we observed no significant differences for steatotic severity after excluding the rats with fibrosis. ARFI elastography may be used to differentiate among degrees of severity of NAFLD and hepatic fibrotic stages in NAFLD rat models.     

Utilizing Contrast-Enhanced Ultrasound Imaging for Evaluating Fatty Liver Disease Progression in Pre-clinical Mouse Models

We developed a protocol to investigate and optimize the application of contrast-enhanced ultrasound (CEUS) to non-invasive diagnosis of progressing fatty liver disease in mouse models. Eighteen 4-wk-old male C57 L/J mice were randomly assigned to one of the three groups and placed on a control diet, high-fat diet or non-alcoholic steatohepatitis diet for the next 10 wk. After 14 wk, B-mode imaging and CEUS imaging using a VisualSonics Vevo2100 system were performed. CEUS imaging and data analysis using three different parameters—peak enhancement, wash-in rate and wash-in perfusion index—revealed a significant decrease in representative blood flow in the high-fat diet group versus controls and a further significant decrease in the non-alcoholic steatohepatitis group (p < 0.001; n?=?6/group). In conclusion, compared with B-mode imaging, non-targeted CEUS imaging was more sensitive in diagnosing early-stage fatty infiltration-mediated vascularity changes in liver parenchyma and provided a more accurate steatohepatitis diagnosis in mouse models.     

弹性酶结合低热量饮食治疗非酒精性脂肪性肝病的临床观察

目的 :评价弹性酶结合低热量饮食在治疗非酒精性脂肪肝 (NAFLD)中的作用。方法选择临床诊断非酒精性脂肪肝病5 0例 ,随机分为治疗组和对照组。治疗组 30例 ,口服弹性酶肠溶片 6 0 0U /次 ,每日 3次 ;对照组 2 0例 ,口服水飞蓟素 ,77mg/次 ,每日 3次 ,两组均结合低热量饮食 ,共治疗 2 4周。治疗前 ,治疗 30d、6 0d分别测定肝功能、肾功能、血脂 ,或肝脏B超。结果 :(1)治疗 6 0d后 ,治疗组丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)、γ -谷氨酰转肽酶 (γ -GT)及碱性磷酸酶 (ALP)比治疗前降低 ,有极显著差异 (P <0 .0 1) ,而对照组治疗前后无显著差异 ,(p >0 .0 5 )。 (2 )治疗 6 0d后 ,治疗组血清胆固醇、甘油三酯比治疗前下降 ,血清高密度脂蛋白则升高 ,有极显著差异 (P <0 .0 5 ) ,但血清低密度脂蛋白无显著差异 ,(p >0 .0 5 )。对照组则上述指标均无显著差异 ,(p >0 .0 5 )。 (3)治疗 6 0d后治疗组与对照组B超脂肪肝消失和好转所占比例分别为 2 0 / 30和 3/ 2 0 (P<0 .0 1)。 (4)治疗 6 0d治疗组与对照组有效率分别为 86 .6 7%和 10 .0 0 % ,有极显著差异 ,(P <0 .0 1)。 (5 )两组均无严重不良反应发生。结论 :弹性酶可减少NAFLD肝脏脂肪沉积 ,降血脂 ,改善肝功能 ,不良反应甚微 ,可作为NAFLD的药物     

2型糖尿病合并非酒精性脂肪性肝病患者血浆脂肪细胞特异性脂肪酸结合蛋白水平的分析

目的研究2型糖尿病（type 2diabetes mellitus,T2DM）合并非酒精性脂肪性肝病（non-alcoholic fattyliver disease,NAFLD）患者血浆脂肪细胞特异性脂肪酸结合蛋白（adipocyte-specific fatty acid-binding protein,A-FABP）的水平及其相关因素。方法 2009年10月～2010年10月选取T2DM合并NAFLD组（A组）60例,未合并NAFLD组56例（B组）为研究对象。测定体质量指数（body mass index,BMI）,检测血脂、糖化血红蛋白（hemoglobinA1c,HbA1c）等生化指标。放射免疫法测定空腹胰岛素（fasting insulin,FINS）,空腹C肽水平（fasting C-peptide,FCP）,计算胰岛素抵抗指数（homeostasis model of assessment-insulin resistance,HOMA-IR）、胰岛素敏感指数（insulin sensitivity index,ISI）,测定A-FABP、C反应蛋白（C-reaction protein,CRP）及肿瘤坏死因子-α（tumor necrosisfactor-α,TNF-α）。结果与B组患者相比,A组患者其血浆A-FABP水平、BMI、腰围、腰臀比、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、CRP、TNF-α、FCP、FINS、总胆固醇、甘油三酯、Ln（HOMA-IR）升高,Ln（ISI）降低,差异有统计学意义（P〈0.05）;两组HbA1c差异无统计学意义（P〉0.05）。A-FABP水平变化与TNF-α、HOMA-IR、CRP呈正相关,与ISI呈负相关。结论 T2DM伴NAFLD中,A-FABP升高与胰岛素抵抗是并存的,且存在明显相关关系,二者在疾病的发生发展中均可能具有重要的作用。     

High frequency ultrasound prediction of mechanical properties of cortical bone with varying amount of mineral content

In this study, we evaluate if high frequency ultrasound impedance measurements can predict the mechanical properties of bones where the amount of bone mineral is varied. The motivation stems from the potential utility of ultrasound as a noninvasive technique to evaluate and monitor the mechanical properties of bone during treatment of diseased states where the ratio of mineral content to organic matrix content could change (e.g., metabolic bone diseases, osteoarthritis, osteogenesis imperfecta, fracture healing). Eleven cortical bovine femur samples, which were taken along the long axis of femur, were used in each group. Bone samples with reduced mineral content (estimated to be 21% and 35% less than the control) were obtained by immersing samples into fluoride ion solution for 3 and 12 d. Control and fluoride treated samples were first tested mechanically in tension. Acoustic impedances of the mechanically tested samples were obtained by using scanning acoustic microscopy (SAM). Results from mechanical tests indicate that the tensile elastic modulus of the samples was highly correlated to the yield strength (r(2) = 0.94, p < 0.01) and to the ultimate strength (r(2) = 0.75, p < 0.01). SAM results indicate that the acoustic impedances were significantly correlated to the elastic modulus (r(2) = 0.85, p < 0.01), yield strength (r(2) = 0.86, p < 0.01) and ultimate strength (r(2) = 0.70, p < 0.01). These results show that ultrasonic techniques could potentially be used to predict the in vivo ultimate strength of bone tissue caused by changes in mineral content.     

CAP对儿童非酒精性脂肪性肝病的诊断价值研究

[目的]探讨CAP对儿童非酒精性脂肪性肝病(NAFLD)的临床诊断价值.[方法]选择2016年8月至2020年9月本院肝病中心收治的91例NAFLD患儿,均经肝脏组织活检,同时进行受控衰减参数(CAP)检查.另选取30例其他肝病患儿为对照组,经肝活检证实无肝脂肪变性,同时也进行CAP检测.运用儿童NAFLD组织学评分系...     

Adaptive Remodeling of Trabecular Bone Core Cultured in 3-D Bioreactor Providing Cyclic Loading: An Acoustic Microscopy Study

Scanning acoustic microscopy (SAM) provides high-resolution mapping of acoustic impedance related to tissue stiffness. This study investigates changes in tissue acoustic impedance resulting from mechanical loading in trabecular bone cores cultured in 3-D bioreactor. Trabecular bone cores were extracted from bovine sternum (n = 15) and ulna metaphysis (n = 15). From each bone, the samples were divided in three groups. The basal control (BC) group was fixed post-extraction, the control (C) and loaded (L) groups were maintained as viable in a controlled culture-loading cell over three weeks. Samples of L group underwent a dynamic compressive strain, whereas C samples were left free from loading. After three weeks, L and C samples were embedded in polymethylmethacrylate and all samples were explored with a 200-MHz SAM. For each specimen, the acoustic impedance distribution was obtained over flat and polished section of bone blocks prepared parallel to the loading axis. Our results showed that in basal controls, the acoustic impedance varied with bone anatomical location and was 15% higher in weight-bearing ulna compared with nonweight-bearing sternum. The comparison between loaded and nonloaded groups showed that sternum-only exhibited significant change in acoustic impedance (L vs. C sternum: +9%). This result suggests that when the applied load is comparable with the stress naturally experienced by a weight-bearing bone (ulna), the tissue material properties (manifested by acoustic impedance) remained unchanged. In conclusion, SAM is a potentially relevant tool for the assessment of subtle changes in intrinsic microelastic properties of bone induced by adaptive remodeling process in response to mechanical loading. (E-mail: amena.saied@upmc.fr)     

超声在评价牛磺酸保护酒精性脂肪肝中的应用

目的通过牛磺酸保护酒精性脂肪肝动物模型实验,对于超声和病理2种效果评价手段进行比较。方法采用白酒灌胃的方式建立大鼠酒精性脂肪肝模型,治疗组分别给予高低2种剂量的牛磺酸,对照组给予生理盐水,实验末进行肝脏超声检查、测量平均动脉压、血清甘油三酯(TG),并对大鼠肝脏进行冷冻切片量化分析。结果与酒精性脂肪肝模型组相比,高低2种浓度的(2%和5%)牛磺酸均可以显著降低酒精性脂肪肝大鼠血清甘油三酯含量(P0.05);高剂量组牛磺酸还能降低酒精性肝损伤大鼠血压(P0.05);肝脏超声量化积分结果表明,高低2种剂量牛磺酸均可显著降低酒精对肝脏的损伤(P0.05),且高低剂量组的保护效果无显著性差异(P0.05),这与冷冻切片量化分析结果相一致。结论牛磺酸能够降低酒精对肝脏的损伤,超声对于诊断和评价酒精性脂肪肝可能具有较高的临床价值。     

水飞蓟宾联合二甲双胍与熊去氧胆酸治疗非酒精性脂肪性肝炎的对比

目的：观察水飞蓟宾联合二甲双胍治疗非酒精性脂肪性肝炎的疗效。方法：106例非酒精性脂肪性肝炎患者,随机分为治疗组（n=53）及对照组（n=53）。治疗组在控制饮食、适当运动基础上给于水飞蓟宾联合二甲双胍治疗;对照组在控制饮食、适当运动基础上给予熊去氧胆酸治疗。全部病例均连续治疗12周。结果：治疗组总有效率,丙氨酸转氨酸（ALT）、天氡氨酸转氨酶（AST）、血糖、三酰甘油（TG）、总胆固醇（TC）下降幅度均优于对照组,差异有统计学意义（P〈0.01）。结论：应用水飞蓟宾联合二甲双胍治疗非酒精性脂肪性肝炎有效,值得临床应用。     

血尿酸与代谢相关脂肪性肝病患者肝功能异常的相关性及因果研究

目的 研究血尿酸(UA)与代谢相关脂肪性肝病(MAFLD)患者肝功能异常的相关性及因果关系。方法 纳入于四川大学华西医院就诊的MAFLD患者98例。用Spearman相关和多元Logistic回归分析UA与丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)间的相关性。用双向孟德尔随机化研究分析UA与ALT、AST之间的因果关系。结果 UA与ALT、AST呈正相关,相关系数分别为0.56(P<0.001)和0.46(P=0.01)。高UA组相较于低UA组ALT(OR=3.58,P=0.003)、AST(OR=3.24,P=0.005)水平增加。正向因果中,UA每升高1标准差(SD),ALT增加0.07SD(P=0.002),AST增加0.06SD(P=0.03)。而在反向因果中,尚未发现ALT、AST与UA间相关(P>0.05)。结论 UA可导致ALT、AST水平升高,是MAFLD患者肝功能受损潜在的危险因素。     

Omega-3必需脂肪酸饮食干预用于治疗干眼症患者的Meta分析

目的探讨Omega-3必需脂肪酸饮食干预用于治疗干眼症患者的干预效果。方法计算机检索Cochrane图书馆、Medline、荷兰医学文摘数据库(the excerpta medica database,EMbase)、Pubmed、护理学数据库(cumulative index to nursing and allied health literature,CINAHL)、中国期刊全文数据库(Chinese national knowledge infrastructure,CNKI)和万方数据库等,收集Omega-3必需脂肪酸饮食干预对于干眼症患者疗效的随机对照试验,并进行文献质量评价和数据提取。结局指标包括类膜破裂时间(tear break-up time,TBUT)、Schirmer试验(Schirmer’s test)、眼表疾病指数(ocular surface disease index,OSDI)。结果最终纳入7篇文献,文献证据质量大多为中等。Meta分析结果显示,Omega-3必需脂肪酸的饮食干预可以有效改善干眼症患者TBUT(MD=0.69S,95%CI:0.281.10)和Schirmer试验(MD=0.74 mm,95%CI:0.291.19)结果,差异有统计学意义(P0.05)。此外,Omega-3必需脂肪酸的饮食干预具有改善OSDI的趋势,但差异无统计学意义(P0.05)。结论Omega-3必需脂肪酸饮食干预可以让干眼症患者获益,但是未来研究中仍然要克服相应的方法学缺陷。     

声学结构定量技术评估乙肝肝纤维化程度的临床价值

目的 通过对乙肝患者肝脏声学结构定量(ASQ)分析与病理及Fibroscan结果对比,初步探讨ASQ技术对乙肝肝纤维化分期的诊断价值.方法 收集在我院确诊为慢性乙型肝炎患者66例,进行ASQ分析和Fibroscan检查,继之行肝脏穿刺活检.结果 随着肝纤维化程度的增加,ASQ定性分析彩色编码图表现为黄绿色区减少,红色区域增加,且不规则;ASQ定量分析图表现为红色曲线峰值变小,蓝色曲线峰值变大,曲线下面积增大.ASQ定量参数BR-Ratio值在各组之间均有显著性差异(P＜0.05)且与肝纤维化分期有较好正相关(r=0.772,P＜0.05),当S≥1、S≥2、S≥3、S≥4时BR-Ratio值的曲线下面积(AUC)分别为0.832、0.913、0.962、0.974; BR-Ratio值区分S≥1、S≥2、S≥3、S≥4的截断值分别为0.33、0.37、0.49、0.55.对ASQ及Fibroscan的AUC进行比较,P均＞0.05.结论 ASQ技术对肝纤维化程度的诊断价值与Fibroscan相近,在肝纤维化定量诊断中具有潜在的临床应用前景.     

Quantification of Liver Viscoelasticity with Acoustic Radiation Force: A Study of Hepatic Fibrosis in a Rat Model

Ultrasound elastography, based on shear wave propagation, enables the quantitative and non-invasive assessment of liver mechanical properties such as stiffness and has been found to be feasible for and useful in the diagnosis of hepatic fibrosis. Most ultrasound elastographic methods use a purely elastic model to describe liver mechanical properties. However, to describe tissue that is dispersive and to obtain an accurate measure of tissue elasticity, the viscoelasticity of the tissue should be examined. The objective of this study was to investigate the shear viscoelastic characteristics, as measured by ultrasound elastography, of liver fibrosis in a rat model and to evaluate the diagnostic accuracy of viscoelasticity for staging liver fibrosis. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl₄); 6 rats served as controls. Liver viscoelasticity was measured in vitro using shear waves induced by acoustic radiation force. The measured mean values of liver elasticity and viscosity ranged from 0.84 to 3.45 kPa and from 1.12 to 2.06 Pa·s for fibrosis stages F0–F4, respectively. Spearman correlation coefficients indicated that stage of fibrosis was well correlated with elasticity (0.88) and moderately correlated with viscosity (0.66). The areas under receiver operating characteristic curves were 0.97 (≥F2), 0.91 (≥F3) and 1.00 (F4) for elasticity and 0.91 (≥F2), 0.79 (≥F3) and 0.74 (F4) for viscosity, respectively. The results confirmed that shear wave velocity was dispersive in frequency, suggesting a viscoelastic model to describe liver fibrosis. The study finds that although viscosity is not as good as elasticity for staging fibrosis, it is important to consider viscosity to make an accurate estimation of elasticity; it may also provide other mechanical insights into liver tissues.     

Effects of n-3 Fatty Acids Supplementation on Plasma Phospholipids Fatty Acid Composition in Patients with Obstructive Jaundice- a Pilot Study

Nutritional and immunological status of patients with obstructive jaundice is usually severely altered, with high mortality rates. The n-3 polyunsaturate fatty acids (PUFA), particularly eicosapentaenoic acid (EPA, 20:5 n-3), posess potent immunomodulatory activities. Thus, our aim was to compare the plasma phospholipid fatty acid (FA) composition of these patients with healthy subjects, as well as before and after 7 days preoperative supplementation with high doses of EPA (0.9 g per day) and docosahexaenoic acid (DHA, 22:6 n-3, 0.6 g per day). We found impaired FA status in obstructive jaundice patients, especially EPA, DHA and PUFA, but significantly increased content of total n-3 FA, 22:5 n-3 FA and particularly EPA, which increased more than 3 fold, after 7 days supplementation. In addition, the n6/n3 ratio significantly decreased from 14.24 to 10.24, demonstrating severely improved plasma phospholipid profile in these patients after the intervention.     

Comparison of Acoustic Radiation Force Impulse Imaging and Transient Elastography for Non-invasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B

The aims of this study were to compare the performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis in patients with chronic hepatitis B and to evaluate the impact of elevated alanine transaminase levels on liver stiffness assessment using ARFI elastography. One hundred eighty consecutive patients with chronic hepatitis B were enrolled in this study and evaluated with respect to histologic and biochemical features. All patients underwent ARFI elastography and TE. ARFI elastography and TE correlated significantly with histologically assessed fibrosis (r = 0.599, p < 0.001, for ARFI elastography; r = 0.628, p < 0.001, for TE) and necro-inflammatory activity (r = 0.591, p < 0.001, for ARFI elastography; r = 0.616, p < 0.001, for TE). Areas under the receiver operating characteristic curves for ARFI elastography and TE were 0.764 and 0.813 (p = 0.302, ≥stage 2), 0.852 and 0.852 (p = 1.000, ≥stage 3) and 0.825 and 0.799 (p = 0.655, S = 4), respectively. The optimum cutoff values for ARFI elastography were 1.63 m/s for stage ≥2, 1.74 m/s for stage ≥3 and 2.00 m/s for stage 4 in patients for whom alanine transaminase levels were evaluated. The cutoff values decreased to 1.24 m/s for ≥ stage 2, 1.32 m/s for ≥ stage 3 and 1.41 m/s for stage 4 in patients with normal alanine transaminase levels. ARFI elastography may be a reliable method for diagnosing the stage of liver fibrosis with diagnostic performance similar to that of TE in patients with chronic hepatitis B. In addition, liver stiffness values obtained with ARFI elastography, like those obtained with TE, may be influenced by alanine transaminase levels.     

Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations

The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.