Toward a Standardization of Ultrasound Scanners for Dynamic Contrast-Enhanced Ultrasonography: Methodology and Phantoms

The standardization of ultrasound scanners for dynamic contrast-enhanced ultrasonography (DCE-US) is mandatory for evaluation of clinical multicenter studies. We propose a robust method using a phantom for measuring the variation of the harmonic signal intensity obtained from the area under the time-intensity curve versus various contrast-agent concentrations. The slope of this measured curve is the calibration parameter. We tested our method on two devices from the same manufacturer (AplioXV and Aplio500, Toshiba, Tokyo, Japan) using the same settings as defined for a French multicenter study. The Aplio500's settings were adjusted to match the slopes of the AplioXV, resulting in the following settings on the Aplio500: at 3.5 MHz: MI = 0.15; CG = 35 dB and at 8 MHz: MI = 0.10; CG = 32 dB. This calibration method is very important for future DCE-US multicenter studies.     

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma.     

Use of Contrast-Enhanced Ultrasound in the Assessment of Uterine Fibroids: A Feasibility Study

Contrast-enhanced ultrasound (CEUS) is an innovative ultrasound technique capable of visualizing both the macro- and microvasculature of tissues. In this prospective pilot study, we evaluated the feasibility of using CEUS to visualize the microvasculature of uterine fibroids and compared CEUS with conventional ultrasound. Four women with fibroids underwent gray-scale ultrasound, sonoelastography and power/color Doppler scans followed by CEUS examination. Analysis of CEUS images revealed initial perfusion of the peripheral rim, that is, a pseudo-capsule, followed by enhancement of the entire lesion through vessels traveling from the exterior to the interior of the fibroid. The pseudo-capsules exhibited slight hyper-enhancement, making a clear delineation of the fibroids possible. The centers of three fibroids exhibited areas lacking vascularization, information not obtainable with the other imaging techniques. CEUS is a feasible technique for imaging and quantifying the microvasculature of fibroids. In comparison with conventional ultrasound imaging modalities, CEUS can provide additional diagnostic information based on the microvasculature.     

Assessment of a New Mathematical Model for the Computation of Numerical Parameters Related to Renal Cortical Blood Flow and Fractional Blood Volume by Contrast-Enhanced Ultrasound

We analyzed the value of a new mathematical model for the quantification of renal cortical blood flow and fractional blood volume by contrast-enhanced ultrasound after the injection of sulfur hexafluoride–filled microbubbles. A vessel-mimicking phantom experiment was preliminarily performed which showed that the effect of microbubble diffusion is negligible compared with the effect of liquid drag. Twelve healthy volunteers (7 male, 5 female; 27 to 48 years [n = 6; group 1], and 61 to 80 years [n = 6; group 2], respectively), with normal renal and cardiac function and not undergoing any pharmacologic treatment, were examined. In each volunteer, both kidneys were scanned after intravenous injection of sulfur hexafluoride–filled microbubbles at a slow rate (4.8 mL at a flow of 4.0 mL/min), and the refill kinetics of the renal cortex after microbubble destruction was evaluated by echo-signal intensity quantification. The progressive replenishment of the renal vessels was approximated both by standard negative exponential function and by the piecewise linear function resulting from our mathematical model. A better dataset approximation was provided by piecewise linear versus standard negative exponential function (overall mean square error: 0.44 vs. 0.51; p < 0.05, Wilcoxon test). The piecewise linear function provided a curve composed of four linear tracts (n = 3 volunteers; 2 from group 1 and 1 from group 2), three linear tracts (n = 6 volunteers; 3 from group 1 and 3 from group 2) or two linear tracts (n = 3 volunteers; 1 from group 1 and 2 from group 2). The piecewise linear function versus standard negative exponential function improved data approximation for the computation of numerical values related to renal cortical blood flow velocity and fractional blood volume. (E-mail: quaia@univ.trieste.it)     

Investigation of the Relationship of Nonlinear Backscattered Ultrasound Intensity with Microbubble Concentration at Low MI

The aim of this study was to measure the relationship of image intensity with contrast agent concentration. In vitro experiments were performed with a flow phantom and a sulphur hexafluoride filled microbubble contrast agent (SonoVue) at different concentrations (0.004‰ to 4‰) covering the range commonly encountered in clinical practice. The concentration of microbubbles in the contrast agent solutions was confirmed optically. Images were collected with a diagnostic ultrasound system (iU22, Phillips Medical Systems, Bothell, WA, USA) and with a nonlinear imaging technique (power modulation) at low mechanical index (MI = 0.05) to avoid bubble destruction. The mean intensity within a region of interest was measured to produce time-intensity curves from linearized (absolute scale) data. The relationship of linearized image intensity to contrast agent concentration was found to be linear up to 1‰ and reached a plateau at approximately 2‰. To operate in the linear range of the intensity-concentration relationship the contrast agent dose should be adjusted to avoid those high values in vivo and the highest dynamic range of the ultrasound system should be used to avoid unnecessary signal saturation. (E-mail: maverk@ucy.ac.cy).     

声学造影与微循环关系的研究

目的 :了解微循环在声学造影中的作用 ,研究声学造影剂与微循环关系。方法 :2 0只家兔分二组 ,分别经兔颈动脉注双氧水、声振白蛋白。结果 :1.二组微循环加权积分双氧水组 14.2 3± 3.31,白蛋白组 15 .18± 5 .40 ,p >0 .0 5 ;2 .兔体内实时测得双氧水气泡直径 16 .6 8± 5 .12μm,声振白蛋白气泡直径 10 .2 3± 0 .98μm,p<0 .0 5 ;3.声学造影气泡始终在微循环中流动。结论 :声学造影剂对微循环有可逆性损害 ,组织器官微循环中气泡多少直接影响声学造影效果。     

超声造影及DSA对肝移植术后脾动脉窃血综合征诊断的对照研究

目的 探讨超声造影对肝移植术后脾动脉窃血综合征的诊断价值.方法 肝移植术后10例患者在超声造影诊断为肝移植术后脾动脉窃血综合征后,即刻进行DSA造影,将两者检查结果进行统计分析.结果 超声造影见移植肝肝动脉内造影剂增强信号微弱,肝动脉内径偏细.DSA造影见肝动脉纤细,造影剂染色稀薄暗淡,脾动脉明显增粗,两者诊断结果无统计学意义.结论 超声造影应常规作为肝移植术后的可疑移植肝血管系统异常的无创检查手段,具有极高的应用价值.     

Automatic Identification of the Optimal Reference Frame for Segmentation and Quantification of Focal Liver Lesions in Contrast-Enhanced Ultrasound

Post-examination interpretation of contrast-enhanced ultrasound (CEUS) cineloops of focal liver lesions (FLLs) requires offline manual assessment by experienced radiologists, which is time-consuming and generates subjective results. Such assessment usually starts by manually identifying a reference frame, where FLL and healthy parenchyma are well-distinguished. This study proposes an automatic computational method to objectively identify the optimal reference frame for distinguishing and hence delineating an FLL, by statistically analyzing the temporal intensity variation across the spatially discretized ultrasonographic image. Level of confidence and clinical value of the proposed method were quantitatively evaluated on retrospective multi-institutional data (n = 64) and compared with expert interpretations. Results support the proposed method for facilitating easier, quicker and reproducible assessment of FLLs, further increasing the radiologists' confidence in diagnostic decisions. Finally, our method yields a useful training tool for radiologists, widening CEUS use in non-specialist centers, potentially leading to reduced turnaround times and lower patient anxiety and healthcare costs.     

Ultrasound Dynamic Micro-Elastography Applied to the Viscoelastic Characterization of Soft Tissues and Arterial Walls

Quantitative noninvasive methods that provide in vivo assessment of mechanical characterization of living tissues, organs and artery walls are of interest because information on their viscoelastic properties in the presence of disease can affect diagnosis and treatment options. This article proposes the dynamic micro-elastography (DME) method to characterize viscoelasticity of small homogeneous soft tissues, as well as the adaptation of the method for vascular applications [vascular dynamic micro-elastography (VDME)]. The technique is based on the generation of relatively high-frequency (240–1100 Hz) monochromatic or transient plane shear waves within the medium and the tracking of these waves from radio-frequency (RF) echoes acquired at 25 MHz with an ultrasound biomicroscope (Vevo 770, Visualsonics). By employing a dedicated shear wave gated strategy during signal acquisition, postprocessed RF sequences could achieve a very high frame rate (16,000 images per s). The proposed technique successfully reconstructed shear wave displacement maps at very high axial (60 μm) and lateral (250 μm) spatial resolutions for motions as low as a few μm. An inverse problem formulated as a least-square minimization, involving analytical simulations (for homogenous and vascular geometries) and experimental measurements were performed to retrieve storage (G′) and loss (G″) moduli as a function of the shearing frequency. Viscoelasticity measurements of agar-gelatin materials and of a small rat liver were proven feasible. Results on a very thin wall (3 mm thickness) mimicking artery enabled to validate the feasibility and the reliability of the vascular inverse problem formulation. Subsequently, the G′ and G″ of a porcine aorta showed that both parameters are strongly dependent on frequency, suggesting that the vascular wall is mechanically governed by complex viscoelastic laws. (E-mail: guy.cloutier@umontreal.ca)     

经阴道超声和三维彩色血管能量成像单用及联用对宫颈癌分期的诊断效能研究

目的 探讨经阴道彩色多普勒超声(TVCDS)、三维彩色血管能量成像(3D-PDUS)单用与联用对宫颈癌分期的诊断效能.方法 选取宫颈癌患者(宫颈癌组)和健康女性(健康组)各68例,两组均接受TVCDS和3D-PDUS检查,比较两组的影像学特征差异.以宫颈癌的病理学分期结果为准,分析TVCDS、3D-PDUS单用与联用对...