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Showing papers in "Ultrasound in Medicine and Biology in 2014"


Journal ArticleDOI
TL;DR: This study indicates that ΔIVC measured with point-of-care ultrasonography is of great value in predicting fluid responsiveness, particularly in patients on controlled mechanical ventilation and those resuscitated with colloids.
Abstract: Respiratory variation in the inferior vena cava (ΔIVC) has been extensively studied with respect to its value in predicting fluid responsiveness, but the results are conflicting. This systematic review was aimed at investigating the diagnostic accuracy of ΔIVC in predicting fluid responsiveness. Databases including Medline, Embase, Scopus and Web of Knowledge were searched from inception to May 2013. Studies exploring the diagnostic performance of ΔIVC in predicting fluid responsiveness were included. To allow for more between- and within-study variance, a hierarchical summary receiver operating characteristic model was used to pool the results. Subgroup analyses were performed for patients on mechanical ventilation, spontaneously breathing patients and those challenged with colloids and crystalloids. A total of 8 studies involving 235 patients were eligible for analysis. Cutoff values of ΔIVC varied across studies, ranging from 12% to 40%. The pooled sensitivity and specificity in the overall population were 0.76 (95% confidence interval [CI]: 0.61-0.86) and 0.86 (95% CI: 0.69-0.95), respectively. The pooled diagnostic odds ratio (DOR) was 20.2 (95% CI: 6.1-67.1). The diagnostic performance of ΔIVC appeared to be better in patients on mechanical ventilation than in spontaneously breathing patients (DOR: 30.8 vs. 13.2). The pooled area under the receiver operating characteristic curve was 0.84 (95% CI: 0.79-0.89). Our study indicates that ΔIVC measured with point-of-care ultrasonography is of great value in predicting fluid responsiveness, particularly in patients on controlled mechanical ventilation and those resuscitated with colloids.

190 citations


Journal ArticleDOI
TL;DR: A new ultrasound-based framework called vector projectile imaging (VPI) that can dynamically render complex flow patterns over an imaging view at millisecond time resolution is presented and suggests that VPI holds promise as a new tool for complex flow analysis.
Abstract: Achieving non-invasive, accurate and time-resolved imaging of vascular flow with spatiotemporal fluctuations is well acknowledged to be an ongoing challenge. In this article, we present a new ultrasound-based framework called vector projectile imaging (VPI) that can dynamically render complex flow patterns over an imaging view at millisecond time resolution. VPI is founded on three principles: (i) high-frame-rate broad-view data acquisition (based on steered plane wave firings); (ii) flow vector estimation derived from multi-angle Doppler analysis (coupled with data regularization and least-squares fitting); (iii) dynamic visualization of color-encoded vector projectiles (with flow speckles displayed as adjunct). Calibration results indicated that by using three transmit angles and three receive angles (-10°, 0°, +10° for both), VPI can consistently compute flow vectors in a multi-vessel phantom with three tubes positioned at different depths (1.5, 4, 6 cm), oriented at different angles (-10°, 0°, +10°) and of different sizes (dilated diameter: 2.2, 4.4 and 6.3 mm; steady flow rate: 2.5 mL/s). The practical merit of VPI was further illustrated through an anthropomorphic flow phantom investigation that considered both healthy and stenosed carotid bifurcation geometries. For the healthy bifurcation with 1.2-Hz carotid flow pulses, VPI was able to render multi-directional and spatiotemporally varying flow patterns (using a nominal frame rate of 416 fps or 2.4-ms time resolution). In the case of stenosed bifurcations (50% eccentric narrowing), VPI enabled dynamic visualization of flow jet and recirculation zones. These findings suggest that VPI holds promise as a new tool for complex flow analysis.

145 citations


Journal ArticleDOI
TL;DR: Good evidence is presented of the ability to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, an advance that should help to set the stage for developing new applications in larger animal models, including humans.
Abstract: Developments in the use of ultrasound to stimulate and modulate neural activity have raised the possibility of using ultrasound as a new investigative and therapeutic tool in brain research. Although the phenomenon of ultrasound-induced neurostimulation has a long history dating back many decades, until now there has been little evidence of a clearly localized effect in the brain, a necessary requirement for the technique to become genuinely useful. Here we report clearly distinguishable effects in sonicating rostral and caudal regions of the mouse motor cortex. Motor responses measured by normalized electromyography in the neck and tail regions changed significantly when sonicating the two different areas of motor cortex. Response latencies varied significantly according to sonication location, suggesting that different neural circuits are activated depending on the precise focus of the ultrasound beam. Taken together, our findings present good evidence of the ability to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, an advance that should help to set the stage for developing new applications in larger animal models, including humans.

117 citations


Journal ArticleDOI
TL;DR: A multi-inclusion phantom experiment showed that the fast shear compounding method could provide a full field-of-view, 2-D and compounded shear elasticity map with three types of inclusions clearly resolved and stiffness measurements showing excellent agreement to the nominal values.
Abstract: A fast shear compounding method was developed in this study using only one shear wave push-detect cycle, such that the shear wave imaging frame rate is preserved and motion artifacts are minimized. The proposed method is composed of the following steps: 1. Applying a comb-push to produce multiple differently angled shear waves at different spatial locations simultaneously; 2. Decomposing the complex shear wave field into individual shear wave fields with differently oriented shear waves using a multi-directional filter; 3. Using a robust 2-D shear wave speed calculation to reconstruct 2-D shear elasticity maps from each filter direction; and 4. Compounding these 2-D maps from different directions into a final map. An inclusion phantom study showed that the fast shear compounding method could achieve comparable performance to conventional shear compounding without sacrificing the imaging frame rate. A multi-inclusion phantom experiment showed that the fast shear compounding method could provide a full field-of-view, 2-D and compounded shear elasticity map with three types of inclusions clearly resolved and stiffness measurements showing excellent agreement to the nominal values.

115 citations


Journal ArticleDOI
TL;DR: Intravascular photoacoustic imaging (IVPA) can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention.
Abstract: The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention.

104 citations


Journal ArticleDOI
TL;DR: SS is an effective method for decreasing shear elastic modulus as well as muscle stiffness and that shear Elastic modulus measurement using the shear wave elastography technique is useful in determining the effects of SS.
Abstract: This study investigated the acute effects of static stretching (SS) on shear elastic modulus as an index of muscle hardness and muscle stiffness and the relationship between change in shear elastic modulus and change in muscle stiffness after SS. The patients were 17 healthy young males. Muscle stiffness was measured during passive ankle dorsiflexion using a dynamometer and ultrasonography before (pre) and immediately after (post) 2 min of SS. In addition, shear elastic modulus was measured by a new ultrasound technique called ultrasonic shear wave elastography. The post-SS values for muscle stiffness and shear elastic modulus were significantly lower than the pre-SS values. In addition, Spearman's rank correlation coefficient indicated a significant correlation between rate of change in shear elastic modulus and rate of change in muscle stiffness. These results suggest that SS is an effective method for decreasing shear elastic modulus as well as muscle stiffness and that shear elastic modulus measurement using the shear wave elastography technique is useful in determining the effects of SS.

101 citations


Journal ArticleDOI
TL;DR: According to the results, the depth range for the most reliable liver stiffness assessment using SWE should be 3-5 cm from the probe surface and simultaneously 1-2 cm below the liver capsule.
Abstract: The purpose of this study was to determine the measurement depth range within which liver stiffness can be reliably assessed using real-time shear wave elastography (SWE) technology. Measurements were performed on phantoms and healthy volunteers. In the first group of patients, measurements were performed at depths of 2–8 cm from the probe surface. In the second group of patients, measurements were conducted 0–7 cm below the liver capsule. Success rate of measurements (SRoM), success rate of patients (SRoS) and coefficients of variation (CVs) of repeated measurements were compared. The SRoMs at 3–7 cm and the CVs at 2–5 cm from the probe surface were significantly higher and lower than those at other depths ( p

84 citations


Journal ArticleDOI
Ji Hyun Youk1, Eun Ju Son1, Hye Mi Gweon1, Hana Kim1, Yun Joo Park1, Jeong-Ah Kim1 
TL;DR: Addition of SE or SWE improved the diagnostic performance of B-mode US, potentially reducing unnecessary biopsies.
Abstract: Our aim was to compare the diagnostic performance of strain elastography (SE) and shear-wave elastography (SWE), combined with B-mode ultrasonography (US), in breast cancer. For 79 breast lesions that underwent SE and SWE, two radiologists reviewed five data sets (B-mode US, SWE, SE and two combined sets). Qualitative and quantitative elastographic data and Breast Imaging Reporting and Data System (BI-RADS) categories were recorded. The area under the receiver operating characteristic curve (AUC) was evaluated. No significant difference in the AUC between the two elastography methods was noted. After subjective assessment by reviewers, the AUC for the combined sets was improved (SWE, 0.987; SE, 0.982; B-mode US, 0.970; p < 0.05). When SE and SWE were added, 38% and 56% of benign BI-RADS category 4a lesions with a low suspicion of cancer were downgraded without false-negative results, respectively. SE and SWE performed similarly. Therefore, addition of SE or SWE improved the diagnostic performance of B-mode US, potentially reducing unnecessary biopsies.

82 citations


Journal ArticleDOI
TL;DR: The results indicated that US can be considered a reliable imaging technique for assessing PF thickness, monitoring the effect of different interventions and guiding therapeutic interventions in patients with PFS.
Abstract: Plantar fasciitis (PFS) is one of the most common causes of heel pain, estimated to affect 10% of the general population during their lifetime. Ultrasound (US) imaging technique is increasingly being used to assess plantar fascia (PF) thickness, monitor the effect of different interventions and guide therapeutic interventions in patients with PFS. The purpose of the present study was to systematically review previously published studies concerning the application of US in the assessment of PF in patients with PFS. A literature search was performed for the period 2000-2012 using the Science Direct, Scopus, PubMed, CINAHL, Medline, Embase and Springer databases. The key words used were: ultrasound, sonography, imaging techniques, ultrasonography, interventional ultrasonography, plantar fascia and plantar fasciitis. The literature search yielded 34 relevant studies. Sixteen studies evaluated the effect of different interventions on PF thickness in patients with PFS using US; 12 studies compared PF thickness between patients with and without PFS using US; 6 studies investigated the application of US as a guide for therapeutic intervention in patients with PFS. There were variations among studies in terms of methodology used. The results indicated that US can be considered a reliable imaging technique for assessing PF thickness, monitoring the effect of different interventions and guiding therapeutic interventions in patients with PFS.

79 citations


Journal ArticleDOI
TL;DR: In this paper, the effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood.
Abstract: The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95–103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker.

77 citations


Journal ArticleDOI
TL;DR: The results from this study indicate that microbubble type and distribution could have significant effects on focused ultrasound-induced BBB opening at lower pressures, but less important effects at higher pressures, possibly because of the stable cavitation that governs the former.
Abstract: Focused ultrasound, in the presence of microbubbles, has been used non-invasively to induce reversible blood-brain barrier (BBB) opening in both rodents and non-human primates This study was aimed at identifying the dependence of BBB opening properties on polydisperse microbubble (all clinically approved microbubbles are polydisperse) type and distribution by using a clinically approved ultrasound contrast agent (Definity microbubbles) and in-house prepared polydisperse (IHP) microbubbles in mice A total of 18 C57 BL/6 mice (n = 3) were used in this study, and each mouse was injected with either Definity or IHP microbubbles via the tail vein The concentration and size distribution of activated Definity and IHP microbubbles were measured, and the microbubbles were diluted to 6 × 10(8)/mL before injection Immediately after microbubble administration, mice were subjected to focused ultrasound with the following parameters: frequency = 15 MHz, pulse repetition frequency = 10 Hz, 1000 cycles, in situ peak rarefactional acoustic pressures = 03, 045 and 06 MPa for a sonication duration of 60 s Contrast-enhanced magnetic resonance imaging was used to confirm BBB opening and allowed for image-based analysis Permeability of the treated region and volume of BBB opening did not significantly differ between the two types of microbubbles (p > 005) at peak rarefractional acoustic pressures of 045 and 06 MPa, whereas IHP microbubbles had significantly higher permeability and opening volume (p < 005) at the relatively lower pressure of 03 MPa The results from this study indicate that microbubble type and distribution could have significant effects on focused ultrasound-induced BBB opening at lower pressures, but less important effects at higher pressures, possibly because of the stable cavitation that governs the former This difference may have become less significant at higher pressures, where inertial cavitation typically occurs

Journal ArticleDOI
TL;DR: Optically characterized the lipid shedding behavior of individual microbubbles on a time scale of nanoseconds to microseconds and found lipid shedding was found to be reproducible, indicating that the shedding event can be controlled.
Abstract: Lipid-coated microbubbles are used clinically as contrast agents for ultrasound imaging and are being developed for a variety of therapeutic applications. The lipid encapsulation and shedding of the lipids by acoustic driving of the microbubble has a crucial role in microbubble stability and in ultrasound-triggered drug delivery; however, little is known about the dynamics of lipid shedding under ultrasound excitation. Here we describe a study that optically characterized the lipid shedding behavior of individual microbubbles on a time scale of nanoseconds to microseconds. A single ultrasound burst of 20 to 1000 cycles, with a frequency of 1 MHz and an acoustic pressure varying from 50 to 425 kPa, was applied. In the first step, high-speed fluorescence imaging was performed at 150,000 frames per second to capture the instantaneous dynamics of lipid shedding. Lipid detachment was observed within the first few cycles of ultrasound. Subsequently, the detached lipids were transported by the surrounding flow field, either parallel to the focal plane (in-plane shedding) or in a trajectory perpendicular to the focal plane (out-of-plane shedding). In the second step, the onset of lipid shedding was studied as a function of the acoustic driving parameters, for example, pressure, number of cycles, bubble size and oscillation amplitude. The latter was recorded with an ultrafast framing camera running at 10 million frames per second. A threshold for lipid shedding under ultrasound excitation was found for a relative bubble oscillation amplitude >30%. Lipid shedding was found to be reproducible, indicating that the shedding event can be controlled.

Journal ArticleDOI
TL;DR: In this article, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions.
Abstract: Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped over the first few pulses ex vivo. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors.

Journal ArticleDOI
TL;DR: The results suggest that tracked ultrasound may become a more tolerable and more accessible alternative to radiographic spine monitoring in adolescent kyphoscoliosis.
Abstract: Monitoring spinal curvature in adolescent kyphoscoliosis requires regular radiographic examinations; however, the applied ionizing radiation increases the risk of cancer. Ultrasound imaging is favored over radiography because it does not emit ionizing radiation. Therefore, we tested an ultrasound system for spinal curvature measurement, with the help of spatial tracking of the ultrasound transducer. Tracked ultrasound was used to localize vertebral transverse processes as landmarks along the spine to measure curvature angles. The method was tested in two scoliotic spine models by localizing the same landmarks using both ultrasound and radiographic imaging and comparing the angles obtained. A close correlation was found between tracked ultrasound and radiographic curvature measurements. Differences between results of the two methods were 1.27 ± 0.84° (average ± SD) in an adult model and 0.96 ± 0.87° in a pediatric model. Our results suggest that tracked ultrasound may become a more tolerable and more accessible alternative to radiographic spine monitoring in adolescent kyphoscoliosis.

Journal ArticleDOI
TL;DR: The fractional Szabo equation, the power law wave equation and the causal fractional Laplacian wave equation are all found to be low-frequency approximations of the fractional Kelvin-Voigt wave equations and the more general fractional Zener wave equation.
Abstract: A set of wave equations with fractional loss operators in time and space are analyzed. The fractional Szabo equation, the power law wave equation and the causal fractional Laplacian wave equation are all found to be low-frequency approximations of the fractional Kelvin-Voigt wave equation and the more general fractional Zener wave equation. The latter two equations are based on fractional constitutive equations, whereas the former wave equations have been derived from the desire to model power law attenuation in applications like medical ultrasound. This has consequences for use in modeling and simulation, especially for applications that do not satisfy the low-frequency approximation, such as shear wave elastography. In such applications, the wave equations based on constitutive equations are the viable ones.

Journal ArticleDOI
TL;DR: This study assesses gradations of steatosis in mouse livers using crawling waves, which are interfering patterns of shear waves introduced into the liver by external sources, and points to the potential of a scoring system for Steatosis based on shear wave dispersion.
Abstract: The accumulation of fat droplets within the liver is an important marker of liver disease. This study assesses gradations of steatosis in mouse livers using crawling waves, which are interfering patterns of shear waves introduced into the liver by external sources. The crawling waves are detected by Doppler ultrasound imaging techniques, and these are analyzed to estimate the shear wave speed as a function of frequency between 200 and 360 Hz. In a study of 70 mice with progressive increases in steatosis from 0% to >60%, increases in steatosis are found to increase the dispersion, or frequency dependence, of shear wave speed. This finding confirms an earlier, smaller study and points to the potential of a scoring system for steatosis based on shear wave dispersion.

Journal ArticleDOI
Zeping Huang1, Jian Zheng1, Jie Zeng1, Xiaoli Wang1, Tao Wu1, Rongqin Zheng1 
TL;DR: The detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V.
Abstract: Real-time shear wave elastography (SWE) is a novel two-dimensional elastographic method that is used to estimate the severity of liver fibrosis. However, the normal range of liver stiffness (LS) and the possible factors that influence SWE are not well understood. The aims of the current study are to define the normal range of LS in healthy subjects and to explore the factors that may affect SWE. A total of 509 healthy subjects underwent SWE to determine the stiffness of their livers, and the effects of gender, age and body mass index (BMI) on LS were analyzed. The effects of different factors on SWE, including the testing position, measurement depth and size of the region of interest (ROI), were analyzed in 137 subjects. SWE imaging was successfully performed in 502 healthy subjects (98.6%, 502/509). The mean value of the SWE measurements in 502 individuals was 5.10 ± 1.02 kPa, and the 95% confidence interval was 5.02-5.19 kPa (range: 2.4-8.7 kPa). We found that the detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V. LS was greater at a depth >5 cm (5.78 ± 1.66 kPa) compared with depths ≤5 cm (4.66 ± 0.77 kPa, p 0.05). The mean LS value in all 502 healthy subjects was 5.10 ± 1.02 kPa. The mean LS value obtained by SWE was not influenced by the size of the ROI, age or BMI, but the mean value was significantly influenced by the different segments of the liver, the detection depth and gender.

Journal ArticleDOI
TL;DR: It is indicated that SWE can quantify Young's modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow.
Abstract: This study assessed inter- and intra-observer reproducibility of shear wave elastography (SWE) measurements in vessel phantoms simulating soft and hard carotid plaque under steady and pulsatile flow conditions. Supersonic SWE was used to acquire cine-loop data and quantify Young's modulus in cryogel vessel phantoms. Data were acquired by two observers, each performing three repeat measurements. Mean Young's modulus was quantified within 2-mm regions of interest averaged across five frames and, depending on vessel model and observer, ranged from 28 to 240 kPa. The mean inter-frame coefficient of variation (CV) was 0.13 (range: 0.07-0.18) for observer 1 and 0.14 (range: 0.12-0.16) for observer 2, with mean intra-class correlation coefficients (ICCs) of 0.84 and 0.83, respectively. The mean inter-operator CV was 0.13 (range: 0.08-0.20), with a mean ICC of 0.76 (range: 0.69-0.82). Our findings indicate that SWE can quantify Young's modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow.

Journal ArticleDOI
TL;DR: LIPUS may affect the integrin-FAK-PI3K/Akt mechanochemical transduction pathway and alter ECM production by OA chondrocytes and aid the future development of a treatment or even cure for OA.
Abstract: The effect of low-intensity pulsed ultrasound (LIPUS) on extracellular matrix (ECM) production via modulation of the integrin/focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been investigated in previous studies in normal chondrocytes, but not in osteoarthritis (OA). Therefore, we investigated the LIPUS-induced integrin β1/FAK/PI3K/Akt mechanochemical transduction pathway in a single study in rabbit OA chondrocytes. Normal and OA chondrocytes were exposed to LIPUS, and mRNA and protein expression of cartilage, metalloproteinases and integrin-FAK-PI3K/Akt signal pathway-related genes was determined by quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Compared with levels in normal chondrocytes, expression levels of ECM-related genes were significantly lower in OA chondrocytes and those of metalloproteinase-related genes were significantly higher. In addition, integrin β1 gene expression and the phosphorylation of FAK, PI3K and Akt were significantly higher in OA chondrocytes. The expression of all tested genes was significantly increased except for that of metalloproteinase, which was significantly decreased in the LIPUS-treated OA group compared to the untreated OA group. LIPUS may affect the integrin-FAK-PI3K/Akt mechanochemical transduction pathway and alter ECM production by OA chondrocytes. Our findings will aid the future development of a treatment or even cure for OA.

Journal ArticleDOI
TL;DR: A hierarchical, supervised learning framework for automatically detecting the standard plane from consecutive 2-D ultrasound images and significantly outperformed both the full abdomen and the separate anatomy detection methods without geometric constraints.
Abstract: Acquisition of the standard plane is crucial for medical ultrasound diagnosis. However, this process requires substantial experience and a thorough knowledge of human anatomy. Therefore it is very challenging for novices and even time consuming for experienced examiners. We proposed a hierarchical, supervised learning framework for automatically detecting the standard plane from consecutive 2-D ultrasound images. We tested this technique by developing a system that localizes the fetal abdominal standard plane from ultrasound video by detecting three key anatomical structures: the stomach bubble, umbilical vein and spine. We first proposed a novel radial component-based model to describe the geometric constraints of these key anatomical structures. We then introduced a novel selective search method which exploits the vessel probability algorithm to produce probable locations for the spine and umbilical vein. Next, using component classifiers trained by random forests, we detected the key anatomical structures at their probable locations within the regions constrained by the radial component-based model. Finally, a second-level classifier combined the results from the component detection to identify an ultrasound image as either a "fetal abdominal standard plane" or a "non- fetal abdominal standard plane." Experimental results on 223 fetal abdomen videos showed that the detection accuracy of our method was as high as 85.6% and significantly outperformed both the full abdomen and the separate anatomy detection methods without geometric constraints. The experimental results demonstrated that our system shows great promise for application to clinical practice.

Journal ArticleDOI
TL;DR: Results indicated that complex intraventricular flow velocity patterns could be quantified using high-frame-rate speckle tracking of both blood and tissue movement, which could potentially help increase diagnostic accuracy and decrease inter-observer variability when measuring peak velocity in shunt flows.
Abstract: High-frame-rate ultrasound speckle tracking was used for quantification of peak velocity in shunt flows resulting from septal defects in congenital heart disease. In a duplex acquisition scheme implemented on a research scanner, unfocused transmit beams and full parallel receive beamforming were used to achieve a frame rate of 107 frames/s for full field-of-view flow images with high accuracy, while also ensuring high-quality focused B-mode tissue imaging. The setup was evaluated in vivo for neonates with atrial and ventricular septal defects. The shunt position was automatically tracked in B-mode images and further used in blood speckle tracking to obtain calibrated shunt flow velocities throughout the cardiac cycle. Validation toward color flow imaging and pulsed wave Doppler with manual angle correction indicated that blood speckle tracking could provide accurate estimates of shunt flow velocities. The approach was less biased by clutter filtering compared with color flow imaging and was able to provide velocity estimates beyond the Nyquist range. Possible placements of sample volumes (and angle corrections) for conventional Doppler resulted in a peak shunt velocity variations of 0.49-0.56 m/s for the ventricular septal defect of patient 1 and 0.38-0.58 m/s for the atrial septal defect of patient 2. In comparison, the peak velocities found from speckle tracking were 0.77 and 0.33 m/s for patients 1 and 2, respectively. Results indicated that complex intraventricular flow velocity patterns could be quantified using high-frame-rate speckle tracking of both blood and tissue movement. This could potentially help increase diagnostic accuracy and decrease inter-observer variability when measuring peak velocity in shunt flows.

Journal ArticleDOI
TL;DR: Simulations of wave propagation in realistic and simplified models of the abdominal wall are used to illustrate the characteristics of coherent and diffuse clutter generated by reverberation and suggest that multi-path scattering from the connective tissue/fat interfaces is a dominant component of reverberation clutter.
Abstract: The degradation of ultrasonic image quality is typically attributed to aberration and reverberation. Although the sources and impact of aberration are well understood, very little is known about the source and impact of image degradation caused by reverberation. Reverberation is typically associated with multiple reflections at two interfaces along the same propagation path, as with the arterial wall or a metal sphere. However, the reverberation that results in image degradation includes more complex interaction between the propagating wave and the tissue. Simulations of wave propagation in realistic and simplified models of the abdominal wall are used to illustrate the characteristics of coherent and diffuse clutter generated by reverberation. In the realistic models, diffuse reverberation clutter is divided into that originating from the tissue interfaces and that originating from sub-resolution diffuse scatterers. In the simplified models, the magnitude of the reverberation clutter is observed as angle and density of the connective tissue are altered. The results suggest that multi-path scattering from the connective tissue/fat interfaces is a dominant component of reverberation clutter. Diffuse reverberation clutter is maximal when the connective tissue is near normal to the beam direction and increases with the density of connective tissue layers at these large angles. The presence of a thick fascial or fibrous layer at the distal boundary of the abdominal wall magnifies the amount of reverberation clutter. The simulations also illustrate that compression of the abdominal layer, a technique often used to mitigate clutter in overweight and obese patients, increases the decay of reverberation clutter with depth. In addition, rotation of the transducer or steering of the beam with respect to highly reflecting boundaries can reduce coherent clutter and transform it to diffuse clutter, which can be further reduced using coherence-based beamforming techniques. In vivo images of the human bladder illustrate some of the reverberation effects observed in simulation.

Journal ArticleDOI
TL;DR: To determine the normal liver stiffness values of healthy children using ARFI with two different probes, 4 C1 and 9 L4, an image-guided ultrasound elastography method that allows quantification of liver stiffness by measurement of shear wave velocity, acoustic radiation force impulse values obtained in the right lobe are determined.
Abstract: Acoustic radiation force impulse (ARFI) is an image-guided ultrasound elastography method that allows quantification of liver stiffness by measurement of shear wave velocity. One purpose of the work described in this article was to determine the normal liver stiffness values of healthy children using ARFI with two different probes, 4 C1 and 9 L4. Another purpose was to evaluate the effects of site of measurement, age, gender and body mass index on liver stiffness values. This prospective study included 60 healthy children (newborn to 14 y) divided into four age groups. One thousand two hundred ARFI measurements were performed, that is, 20 measurements per patient (5 measurements in each lobe, with each probe). Means, standard deviations (SD) and confidence intervals for velocity were calculated for each hepatic lobe and each probe in each age group and for the whole group. Mean shear wave velocity measured in the right lobe was 1.19 ± 0.04 m/s (SD = 0.13) with the 4 C1 transducer and 1.15 ± 0.04 m/s (SD = 0.15) with the 9 L4 transducer. Age had a small effect on shear wave measurements. Body mass index and sex had no significant effects on ARFI values, whereas site of measurement had a significant effect, with lower ARFI values in the right hepatic lobe. ARFI is a non-invasive technique that is feasible to perform in children with both the 4 C1 and 9 L4 probes. The aforementioned velocity values obtained in the right lobe may be used as reference values for normal liver stiffness in children.

Journal ArticleDOI
TL;DR: Two-point AT length underestimated centroid AT length by 0.7 mm, suggesting that the effect of curvature on in vivo AT length is negligible, and three-dimensional ultrasound provided accurate measures of phantom volume and length.
Abstract: This study investigated the accuracy of phantom volume and length measurements and the reliability of in vivo Achilles tendon (AT) volume, length and cross-sectional area measurements obtained using freehand 3-D ultrasound. Participants (n = 13) were scanned on consecutive days under active and passive loading conditions. In vivo AT length was evaluated using a two-point method and an approach that accounted for AT curvature (centroid method). Three-dimensional ultrasound provided accurate measures of phantom volume and length (mean difference = 0.05 mL and 0.2 mm, respectively) and reliable in vivo measures of AT volume, length and average cross-sectional area, with all intra-class correlations coefficients greater than 0.98. The mean minimally detectable changes for in vivo AT volume, two-point length and centroid length were 0.2 mL, 1.5 mm and 2.0 mm, respectively. Two-point AT length underestimated centroid AT length by 0.7 mm, suggesting that the effect of curvature on in vivo AT length is negligible.

Journal ArticleDOI
TL;DR: Observations suggest that a direct mechanical effect of oscillating lipid microbubbles on an adjacent thrombus may play a role in mediating clot disruption in the presence of specific ultrasound conditions.
Abstract: Thrombotic arterial occlusion is the principal etiology for acute cardiovascular syndromes such as stroke, myocardial infarction and unstable angina. Exposing the thrombus to ultrasound and microbubbles facilitates thrombus disruption, making “sonothrombolysis” a potentially powerful therapeutic strategy for thromboembolic diseases. However, optimization of such a strategy, and hence clinical translation, is constrained by an incomplete understanding of mechanisms by which ultrasound-induced microbubble vibrations disrupt blood clots. We posit that previously reported sonothrombolytic efficacy using inertial cavitation regimes was due, at least in part, to mechanical clot disruption by oscillating microbubbles. To test this hypothesis, we optically characterized lipid microbubble interactions with thrombus in the presence of ultrasound using a recently developed ultra-high-speed microscopy imaging system to visualize microbubble acoustic behaviors at megahertz frame rates. A microscope/acoustic stage designed for the system allowed an experimentally created thrombus and microbubbles to be insonified at a co-localized acoustic and optical focus during synchronized high-speed imaging. Under inertial cavitation conditions, large-amplitude microbubble oscillations caused thrombus deformation and pitting. Acoustic radiation forces (Bjerknes forces) further augmented microbubble-thrombus interaction. These observations suggest that a direct mechanical effect of oscillating lipid microbubbles on an adjacent thrombus may play a role in mediating clot disruption in the presence of specific ultrasound conditions.

Journal ArticleDOI
TL;DR: The results indicate that adding castor oil to gelatin phantoms decreases shear modulus, but increases shear wave dispersion, and the phantom recipe developed in this study can be used in validating ultrasound shearWave elastography techniques for soft tissues.
Abstract: Because tissues consist of solid and fluid materials, their mechanical properties should be characterized in terms of both elasticity and viscosity. Although the elastic properties of tissue-mimicking phantoms have been extensively studied and well characterized in commercially available phantoms, their viscous properties have not been fully investigated. In this article, a set of 14 tissue-mimicking phantoms with different concentrations of gelatin and castor oil were fabricated and characterized in terms of acoustic and viscoelastic properties. The results indicate that adding castor oil to gelatin phantoms decreases shear modulus, but increases shear wave dispersion. For 3% gelatin phantoms containing 0%, 10%, 20% and 40% oil, the measured shear moduli are 2.01 ± 0.26, 1.68 ± 0.25, 1.10 ± 0.22 and 0.88 ± 0.17 kPa, and the Voigt-model coupled shear viscosities are 0.60 ± 0.11, 0.89 ± 0.07, 1.05 ± 0.11 and 1.06 ± 0.13 Pa·s, respectively. The results also confirm that increasing the gelatin concentration increases shear modulus. For phantoms containing 3%, 4%, 5%, 6% and 7% gelatin, the measured shear moduli are 2.01 ± 0.26, 3.10 ± 0.34, 4.18 ± 0.84, 8.05 ± 1.00 and 10.24 ± 1.80 kPa at 0% oil and 1.10 ± 0.22, 1.97 ± 0.20, 3.13 ± 0.63, 4.60 ± 0.60 and 8.43 ± 1.39 kPa at 20% oil, respectively. The phantom recipe developed in this study can be used in validating ultrasound shear wave elastography techniques for soft tissues.

Journal ArticleDOI
TL;DR: Preliminary experiments indicated that damage was confined to the ultrasonic focus, suggesting that tolerable treatments would be possible with a more tightly focused hemispheric array that allows the whole focus to be placed inside of the main arteries in the human brain.
Abstract: The purpose of this study was to evaluate use of intravascular perfluorocarbon droplets to reduce the sonication power required to achieve clot lysis with high-intensity focused ultrasound. High-intensity focused ultrasound with droplets was initially applied to blood clots in an in vitro flow apparatus, and inertial cavitation thresholds were determined. An embolic model for ischemic stroke was used to illustrate the feasibility of this technique in vivo. Recanalization with intravascular droplets was achieved in vivo at 24 ± 5% of the sonication power without droplets. Recanalization occurred in 71% of rabbits that received 1-ms pulsed sonications during continuous intravascular droplet infusion (p = 0.041 vs controls). Preliminary experiments indicated that damage was confined to the ultrasonic focus, suggesting that tolerable treatments would be possible with a more tightly focused hemispheric array that allows the whole focus to be placed inside of the main arteries in the human brain.

Journal ArticleDOI
TL;DR: Doppler vortography is a potentially promising echocardiographic tool for quantification of vortex flow in the left ventricle and is tested in patients and compared with vector flow mapping by eChocardiography.
Abstract: We propose a new approach to quantification of intracardiac vorticity based on conventional color Doppler images —Doppler vortography. Doppler vortography relies on the centrosymmetric properties of the vortices.Such properties induce particular symmetriesin the Doppler flow data that can be exploited to describe thevorticesquantitatively.Forthispurpose,akernelfilterwasdeveloped toderive aparameter,theblood vortex signature (BVS), that allows detection of the main intracardiac vortices and estimation of their core vorticities. The reliability of Doppler vortography was assessed in mock Doppler fields issued from simulations and in vitro data. Doppler vortography was also tested in patients and compared with vector flow mapping by echocardiog- raphy. Strongcorrelations were obtained between Dopplervortography-derivedandground-truthvorticities(in silico: r 2 5 0.98, in vitro: r 2 5 0.86, in vivo: r 2 5 0.89). Our results indicate that Doppler vortography is a poten- tially promising echocardiographic tool for quantification of vortex flow in the left ventricle. (E-mail: damien. garcia@crchum.qc.ca or garcia.damien@gmail.com) 2014 World Federation for Ultrasound in Medicine & Biology.

Journal ArticleDOI
TL;DR: UFR-TDI provided additional information in early and late systole: in all subjects, the method was able to separate the timing of electrical activation, start of mechanical contraction, mitral valve closure and start of ejection.
Abstract: We describe a new tissue Doppler imaging (TDI) method, ultra-high frame rate tissue Doppler imaging (UFR-TDI). With two broad transmit beams covering only the ventricular walls, we achieve 1200 frames/s in a four-chamber apical view. We examined 10 healthy volunteers to study the feasibility of this method. Ultra-high-frame-rate TDI provided peak annular velocities and time to peak S' intervals in good agreement with those measured with conventional TDI. Moreover, UFR-TDI provided additional information in early and late systole: In all subjects, the method was able to separate the timing of electrical activation, start of mechanical contraction, mitral valve closure and start of ejection. The earliest mechanical activation was seen before mitral valve closure. The method was also able to measure the propagation speed of the mechanical wave created by aortic valve closure.

Journal ArticleDOI
TL;DR: The purpose of this study was to evaluate the deformation and displacement of the normal median nerve at the proximal carpal tunnel level on transverse ultrasound images during different wrist movements, to have a baseline for comparison with abnormal movements.
Abstract: The symptoms of carpal tunnel syndrome, a compression neuropathy of the median nerve at the wrist, are aggravated by wrist motion, but the effect of these motions on median nerve motion are unknown. To better understand the biomechanics of the abnormal nerve, it is first necessary to understand normal nerve movement. The purpose of this study was to evaluate the deformation and displacement of the normal median nerve at the proximal carpal tunnel level on transverse ultrasound images during different wrist movements, to have a baseline for comparison with abnormal movements. Dynamic ultrasound images of both wrists of 10 asymptomatic volunteers were obtained during wrist maximal flexion, extension and ulnar deviation. To simplify the analysis, the initial and final shape and position of the median nerve were measured and analyzed. The circularity of the median nerve was significantly increased and the aspect ratio and perimeter were significantly decreased in the final image compared with the first image during wrist flexion with finger extension, wrist flexion with finger flexion and wrist ulnar deviation with finger extension (p < 0.01). There were significant differences in median nerve displacement vector between finger flexion, wrist flexion with finger extension and wrist ulnar deviation with finger extension (all p's < 0.001). The mean amplitudes of median nerve motion in wrist flexion with finger extension (2.36 ± 0.79 normalized units [NU]), wrist flexion with finger flexion (2.46 ± 0.84 NU) and wrist ulnar deviation with finger extension (2.86 ± 0.51 NU) were higher than those in finger flexion (0.82 ± 0.33 NU), wrist extension with finger extension (0.77 ± 0.46 NU) and wrist extension with finger flexion (0.81 ± 0.58 NU) (p < 0.0001). In the normal carpal tunnel, wrist flexion and ulnar deviation could induce significant transverse displacement and deformation of the median nerve.