Focused ultrasound and microbubbles for enhanced extravasation.

PubMed

Böhmer, M R; Chlon, C H T; Raju, B I; Chin, C T; Shevchenko, T; Klibanov, A L

2010-11-20

The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

[Contrast-enhanced ultrasound in animal models].

PubMed

Paprottka, P M; Zengel, P; Ingrisch, M; Cyran, C C; Eichhorn, M; Reiser, M F; Nikolaou, K; Clevert, D-A

2011-06-01

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

Tissue mimicking simulations for temporal enhanced ultrasound-based tissue typing

NASA Astrophysics Data System (ADS)

Bayat, Sharareh; Imani, Farhad; Gerardo, Carlos D.; Nir, Guy; Azizi, Shekoofeh; Yan, Pingkun; Tahmasebi, Amir; Wilson, Storey; Iczkowski, Kenneth A.; Lucia, M. Scott; Goldenberg, Larry; Salcudean, Septimiu E.; Mousavi, Parvin; Abolmaesumi, Purang

2017-03-01

Temporal enhanced ultrasound (TeUS) is an imaging approach where a sequence of temporal ultrasound data is acquired and analyzed for tissue typing. Previously, in a series of in vivo and ex vivo studies we have demonstrated that, this approach is effective for detecting prostate and breast cancers. Evidences derived from our experiments suggest that both ultrasound-signal related factors such as induced heat and tissue-related factors such as the distribution and micro-vibration of scatterers lead to tissue typing information in TeUS. In this work, we simulate mechanical micro-vibrations of scatterers in tissue-mimicking phantoms that have various scatterer densities reflecting benign and cancerous tissue structures. Finite element modeling (FEM) is used for this purpose where the vertexes are scatterers representing cell nuclei. The initial positions of scatterers are determined by the distribution of nuclei segmented from actual digital histology scans of prostate cancer patients. Subsequently, we generate ultrasound images of the simulated tissue structure using the Field II package resulting in a temporal enhanced ultrasound. We demonstrate that the micro-vibrations of scatterers are captured by temporal ultrasound data and this information can be exploited for tissue typing.

Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances

PubMed Central

Xu, Shi; Olenyuk, Bogdan Z.; Okamoto, Curtis T.; Hamm-Alvarez, Sarah F.

2012-01-01

Targeting of drugs and their carrier systems by using receptor-mediated endocytotic pathways was in its nascent stages 25 years ago. In the intervening years, an explosion of knowledge focused on design and synthesis of nanoparticulate delivery systems as well as elucidation of the cellular complexity of what was previously-termed receptor-mediated endocytosis has now created a situation when it has become possible to design and test the feasibility of delivery of highly specific nanoparticle drug carriers to specific cells and tissue. This review outlines the mechanisms governing the major modes of receptor-mediated endocytosis used in drug delivery and highlights recent approaches using these as targets for in vivo drug delivery of nanoparticles. The review also discusses some of the inherent complexity associated with the simple shift from a ligand-drug conjugate versus a ligand-nanoparticle conjugate, in terms of ligand valency and its relationship to the mode of receptor-mediated internalization. PMID:23026636

New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

NASA Astrophysics Data System (ADS)

Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

2008-05-01

The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo study

PubMed Central

2014-01-01

Background The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye. Methods An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm2 and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor samples, collected 90 min after the treatment, was determined using chromatography methods. Light microscopy observations were done to determine the structural changes in the cornea as a result of ultrasound application. Results An increase in drug concentration in aqueous humor samples of 2.8 times (p < 0.05) with ultrasound application at 400 kHz and 2.4 times (p < 0.01) with ultrasound application at 600 kHz was observed as compared to sham-treated samples. Histological analysis showed that the structural changes in the corneas exposed to ultrasound predominantly consisted of minor epithelial disorganization. Conclusions Ultrasound application enhanced the delivery of an anti-inflammatory ocular drug, dexamethasone sodium phosphate, through the cornea in vivo. Ultrasound-enhanced ocular drug delivery appears to be a promising area of research with a potential future application in a clinical setting. PMID:24921047

Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity.

PubMed

Zhao, Xiaochen; Li, Lu; Zhao, Hongzhi; Li, Tao; Wu, Shengzheng; Zhong, Yu; Zhao, Yang; Liu, Zheng

2012-02-01

To explore the haemostatic effects of microbubble-enhanced ultrasound (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits. Liver incisions made on 20 rabbits were treated with a pulsed therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an acoustic intensity of 0.4 W/cm(2). The treatment was coordinated with intravenous injection of microbubbles. Ultrasound only and sham treatment served as the controls. Visual bleeding score and 10-min bleeding volume were evaluated for haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess the liver perfusion. Nine treated livers were harvested for acute histological examination. Regarding the bleeding incisions made on rabbit livers, the haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding continued in the controls treated by ultrasound or microbubble injection alone. The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in the MEUS group compared with those of the controls (p < 0.01). The mechanism of MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the haemorrhage of the portal area, which formed a joint compression on the regional liver circulation. Low acoustic intensity MEUS might provide a novel method for liver haemostasis. • This animal experiment demonstrates a novel method of controlling hepatic haemorrhage • The treatment uses therapeutic ultrasound during enhancement with intravenous microbubbles • This combined therapy was more effective than ultrasound or intravenous microbubbles alone • More work is required with larger animals before potential human trials.

Contrast-enhanced ultrasound (CEUS) in blunt abdominal trauma

PubMed Central

Piccolo, Claudia Lucia; Galluzzo, Michele; Ianniello, Stefania; Sessa, Barbara; Trinci, Margherita

2016-01-01

Baseline ultrasound is essential in the early assessment of patients with a huge haemoperitoneum undergoing an immediate abdominal surgery; nevertheless, even with a highly experienced operator, it is not sufficient to exclude parenchymal injuries. More recently, a new ultrasound technique using second generation contrast agents, named contrast-enhanced ultrasound (CEUS) has been developed. This technique allows all the vascular phase to be performed in real time, increasing ultrasound capability to detect parenchymal injuries, enhancing some qualitative findings, such as lesion extension, margins and its relationship with capsule and vessels. CEUS has been demonstrated to be almost as sensitive as contrast-enhanced CT in the detection of traumatic injuries in patients with low-energy isolated abdominal trauma, with levels of sensitivity and specificity up to 95%. Several studies demonstrated its ability to detect lesions occurring in the liver, spleen, pancreas and kidneys and also to recognize active bleeding as hyperechoic bands appearing as round or oval spots of variable size. Its role seems to be really relevant in paediatric patients, thus avoiding a routine exposure to ionizing radiation. Nevertheless, CEUS is strongly operator dependent, and it has some limitations, such as the cost of contrast media, lack of panoramicity, the difficulty to explore some deep regions and the poor ability to detect injuries to the urinary tract. On the other hand, it is timesaving, and it has several advantages, such as its portability, the safety of contrast agent, the lack to ionizing radiation exposure and therefore its repeatability, which allows follow-up of those traumas managed conservatively, especially in cases of fertile females and paediatric patients. PMID:26607647

Rayleigh-maximum-likelihood bilateral filter for ultrasound image enhancement.

PubMed

Li, Haiyan; Wu, Jun; Miao, Aimin; Yu, Pengfei; Chen, Jianhua; Zhang, Yufeng

2017-04-17

Ultrasound imaging plays an important role in computer diagnosis since it is non-invasive and cost-effective. However, ultrasound images are inevitably contaminated by noise and speckle during acquisition. Noise and speckle directly impact the physician to interpret the images and decrease the accuracy in clinical diagnosis. Denoising method is an important component to enhance the quality of ultrasound images; however, several limitations discourage the results because current denoising methods can remove noise while ignoring the statistical characteristics of speckle and thus undermining the effectiveness of despeckling, or vice versa. In addition, most existing algorithms do not identify noise, speckle or edge before removing noise or speckle, and thus they reduce noise and speckle while blurring edge details. Therefore, it is a challenging issue for the traditional methods to effectively remove noise and speckle in ultrasound images while preserving edge details. To overcome the above-mentioned limitations, a novel method, called Rayleigh-maximum-likelihood switching bilateral filter (RSBF) is proposed to enhance ultrasound images by two steps: noise, speckle and edge detection followed by filtering. Firstly, a sorted quadrant median vector scheme is utilized to calculate the reference median in a filtering window in comparison with the central pixel to classify the target pixel as noise, speckle or noise-free. Subsequently, the noise is removed by a bilateral filter and the speckle is suppressed by a Rayleigh-maximum-likelihood filter while the noise-free pixels are kept unchanged. To quantitatively evaluate the performance of the proposed method, synthetic ultrasound images contaminated by speckle are simulated by using the speckle model that is subjected to Rayleigh distribution. Thereafter, the corrupted synthetic images are generated by the original image multiplied with the Rayleigh distributed speckle of various signal to noise ratio (SNR) levels and

Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

PubMed

Medellin-Kowalewski, Alexandra; Wilkens, Rune; Wilson, Alexandra; Ruan, Ji; Wilson, Stephanie R

2016-01-01

The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global

Comparison of gadobenate dimeglumine-enhanced breast MRI and gadopentetate dimeglumine-enhanced breast MRI with mammography and ultrasound for the detection of breast cancer.

PubMed

Gilbert, Fiona J; van den Bosch, Harrie C M; Petrillo, Antonella; Siegmann, Katja; Heverhagen, Johannes T; Panizza, Pietro; Gehl, Hans-Björn; Pediconi, Federica; Diekmann, Felix; Peng, Wei-Jun; Ma, Lin; Sardanelli, Francesco; Belli, Paolo; Corcione, Stefano; Zechmann, Christian M; Faivre-Pierret, Matthieu; Martincich, Laura

2014-05-01

To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue. In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3–5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared. In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8–17.5%; P < 0.0001), ultrasound (Δ18.3–20.0%; P < 0.0001), and mammography and/or ultrasound (Δ8.6–10.7%; P ≤ 0.0105) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0–5.5% vs. 11.1% at mammography; 6.3–8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2–97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2–84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2–96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7–88.5% on gadopentetate

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.

PubMed

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-08-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a "smart needle" to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure.

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain

PubMed Central

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-01-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a “smart needle” to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure. PMID:23927197

Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.

PubMed

Kwok, Sheldon J J; El Kaffas, Ahmed; Lai, Priscilla; Al Mahrouki, Azza; Lee, Justin; Iradji, Sara; Tran, William Tyler; Giles, Anoja; Czarnota, Gregory J

2013-11-01

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Biliary lithotripsy can be enhanced with proper ultrasound probe position.

PubMed

Affronti, J; Flournoy, T; Akers, S; Baillie, J

1992-04-01

We have demonstrated in our in vitro system that an extracorporeal lithotripter utilizing a movable ultrasound probe can fragment gallstones more effectively when the ultrasound probe is not partially blocking shock waves. Using a pressure transducer we measured the pressures in the focal volume of a Wolf Piezolith 2300 lithotripter with the ultrasound probe fully extended and fully retracted. We also chose 12 pairs of twin gallstones, each taken from the same gallbladder. One stone from each pair was subjected to shock waves while the ultrasound probe was fully extended and the other treated while the probe was fully retracted. Shock wave pressures (which are converted to a measurable voltage output by our transducer) were clearly lower when the ultrasound probe was extended (5.45 volts; SEM = 0.10 volts) as compared to when the ultrasound scanner was retracted (6.7 volts: SEM = 0.08 volts). Significantly more shock waves were required to completely fragment stones when the ultrasound scanner was extended than when it was retracted (p = 0.01 using the nonparametric Wilcoxon's signed rank test). These results show that, in the lithotripter tested, an extended in-line ultrasound scanner can partially block shock waves. Retraction of an extendible ultrasound probe may enhance stone fragmentation when operating at the highest shock wave intensity.

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

PubMed

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction.

PubMed

Ivancevich, Nikolas M; Pinton, Gianmarco F; Nicoletto, Heather A; Bennett, Ellen; Laskowitz, Daniel T; Smith, Stephen W

2008-09-01

Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3-D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3-D contrast-enhanced transcranial ultrasound. Using real-time 3-D (RT3D) ultrasound and microbubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and nine via the suboccipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the suboccipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44%, the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology.

Real-Time 3D Contrast-Enhanced Transcranial Ultrasound and Aberration Correction

PubMed Central

Ivancevich, Nikolas M.; Pinton, Gianmarco F.; Nicoletto, Heather A.; Bennett, Ellen; Laskowitz, Daniel T.; Smith, Stephen W.

2008-01-01

Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3D contrast-enhanced transcranial ultrasound. Using real-time 3D (RT3D) ultrasound and micro-bubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and 9 via the sub-occipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the sub-occipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44% the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology. PMID:18395321

Disruption of Prostate Microvasculature by Combining Microbubble-Enhanced Ultrasound and Prothrombin

PubMed Central

Liu, Yongliang; Qiao, Lu; Gao, Wenhong; Zhang, Weiguo; Liu, Zheng

2016-01-01

Previous studies have shown a unique method to disrupt tumor vasculature using pulsed, high-pressure amplitude therapeutic ultrasound combined with microbubbles. In this study, we attempted to destroy the prostate vasculature of canine prostates using microbubble-enhanced ultrasound (MEUS) and prothrombin. The prostates of 43 male mongrel canines were surgically exposed. Twenty-two prostates were treated using MEUS (n = 11) or MEUS and prothrombin (PMEUS, n = 11). The other 21 prostates, which were treated using microbubbles (n = 7), ultrasound (n = 7) or prothrombin (n = 7) only, served as the controls. Prothrombin was intravenously infused at 20 IU/kg. MEUS was induced using a therapeutic ultrasound device at a peak negative pressure of 4.47 MPa and a microbubble injection. Contrast-enhanced ultrasound was performed to assess the blood perfusion of the prostates. Then, the prostate tissue was harvested immediately after treatment and at 48 hours later for pathological examination. The contrast-enhanced ultrasound peak value of the prostate decreased significantly from 36.2 ± 5.6 to 27.1 ± 6.3 after treatment in the PMEUS group, but it remained unchanged in the other groups. Histological examination found severe microvascular rupture, hemorrhage and thrombosis in both MEUS- and PMEUS-treated prostates immediately after treatment, while disruption in the PMEUS group was more severe than in the MEUS group. Forty-eight hours after treatment, massive necrosis and infiltration of white blood cells occurred in the PMEUS group. This study demonstrated that PMEUS disrupted the normal microvasculature of canine prostates and induced massive necrosis. PMEUS could potentially become a new noninvasive method used for the treatment of benign prostatic hyperplasia. PMID:27643992

Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

NASA Astrophysics Data System (ADS)

Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

2009-04-01

Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (p<0.001). There was no significant improvement in survival between those who received stand-alone chemotherapy and those who did not receive any treatment (p>0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

Enhanced Lesion Visualization in Image-Guided Noninvasive Surgery With Ultrasound Phased Arrays

DTIC Science & Technology

2001-10-25

81, 1995. [4] N. Sanghvi et al., “Noninvasive surgery of prostate tissue by high-intensity focused ultrasound ,” IEEE Trans. UFFC, vol. 43, no. 6, pp...ENHANCED LESION VISUALIZATION IN IMAGE-GUIDED NONINVASIVE SURGERY WITH ULTRASOUND PHASED ARRAYS Hui Yao, Pornchai Phukpattaranont and Emad S. Ebbini...Department of Electrical and Computer Engineering University of Minnesota Minneapolis, MN 55455 Abstract- We describe dual-mode ultrasound phased

Scale-up of an ultrasound-enhanced bioscouring process

USDA-ARS?s Scientific Manuscript database

Using previously determined optimized reaction conditions, an ultrasound-enhanced bioscouring process was scaled to ten gallon capacity and a system of rollers was added which allowed for continuous fabric feed and equipment operation. UV-Vis photospectroscopic data from bioscoured fabric samples co...

Microbubble-enhanced ultrasound to demonstrate urethral transection in a case of penile fracture.

PubMed

Czarnecki, Oliver; von Stempel, Conrad Brice; Sangster, Pippa; Walkden, Miles

2017-09-23

A 47-year-old man attended the emergency department following trauma during sexual intercourse after which he developed penile swelling and haematuria several hours later. A penile fracture was suspected but given the slightly atypical history, ultrasound was performed to look for a fracture. Given the history of haematuria, both a standard Doppler ultrasound and a microbubble-enhanced retrograde ultrasound urethrogram were performed. The Doppler confirmed the suspected diagnosis of penile fracture, and microbubble urethrogram demonstrated a urethral injury. This facilitated prompt surgical treatment and helped guide the surgical approach. Retrograde microbubble enhanced ultrasound urethrogram is a novel technique that can be used in conjunction with standard ultrasound to confirm the presence of a concurrent urethral rupture in penile fracture. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Enhanced cytotoxic effect of cisplatin using diagnostic ultrasound and microbubbles in vitro

NASA Astrophysics Data System (ADS)

Sasaki, Noboru; Nakamura, Kensuke; Murakami, Masahiro; Lim, Sue Yee; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2012-10-01

Diagnostic ultrasound has accomplished drug and gene delivery by ultrasound targeted microbubble destruction (UTMD). However, the efficacy of delivery is still relatively low. Therefore, we optimized conditions of UTMD using diagnostic ultrasound and ultrasound contrast agent microbubbles. Canine thyroid adenocarcinoma cells were cultured in a 96-well plate. After addition of cisplatin and Sonazoid®, the plate was inverted to raise microbubbles near cells and incubated. Cells were exposed to diagnostic ultrasound using a linear probe operated in the contrast harmonic imaging mode. The center frequency was 2.5 MHz with a mechanical index of 1.33 and a frame rate of 48 frames/sec. Cytotoxic effect of cisplatin was evaluated 24h after exposure using trypan blue dye exclusion test. We optimized incubation duration, cisplatin concentration, and the relationship between microbubble concentration and exposure duration. The optimum enhancement was observed at incubation duration of 5min, cisplatin concentration of 1 μg/ml, and microbubble concentration of 2.4 × 105 microbubbles/ml. Exposure duration did not influence the enhancement at the microbubble concentration of 2.4 × 105 microbubbles/ml. Our results suggest that relative low concentrations of drug and microbubbles with short exposure duration might be sufficient for drug delivery by UTMD using diagnostic ultrasound.

[Contrast-enhanced ultrasound (CEUS) and image fusion for procedures of liver interventions].

PubMed

Jung, E M; Clevert, D A

2018-06-01

Contrast-enhanced ultrasound (CEUS) is becoming increasingly important for the detection and characterization of malignant liver lesions and allows percutaneous treatment when surgery is not possible. Contrast-enhanced ultrasound image fusion with computed tomography (CT) and magnetic resonance imaging (MRI) opens up further options for the targeted investigation of a modified tumor treatment. Ultrasound image fusion offers the potential for real-time imaging and can be combined with other cross-sectional imaging techniques as well as CEUS. With the implementation of ultrasound contrast agents and image fusion, ultrasound has been improved in the detection and characterization of liver lesions in comparison to other cross-sectional imaging techniques. In addition, this method can also be used for intervention procedures. The success rate of fusion-guided biopsies or CEUS-guided tumor ablation lies between 80 and 100% in the literature. Ultrasound-guided image fusion using CT or MRI data, in combination with CEUS, can facilitate diagnosis and therapy follow-up after liver interventions. In addition to the primary applications of image fusion in the diagnosis and treatment of liver lesions, further useful indications can be integrated into daily work. These include, for example, intraoperative and vascular applications as well applications in other organ systems.

Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.

PubMed

Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

2012-11-01

The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements

ULTRASOUND-ENHANCED rt-PA THROMBOLYSIS IN AN EX VIVO PORCINE CAROTID ARTERY MODEL

PubMed Central

Hitchcock, Kathryn E.; Ivancevich, Nikolas M.; Haworth, Kevin J.; Caudell Stamper, Danielle N.; Vela, Deborah C.; Sutton, Jonathan T.; Pyne-Geithman, Gail J.; Holland, Christy K.

2014-01-01

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. PMID:21723448

Ceramic membrane ultrafiltration of natural surface water with ultrasound enhanced backwashing.

PubMed

Boley, A; Narasimhan, K; Kieninger, M; Müller, W-R

2010-01-01

Ultrafiltration membrane cleaning with ultrasound enhanced backwashing was investigated with two ceramic membrane systems in parallel. One of them was subjected to ultrasound during backwashing, the other acted as a reference system. The feed water was directly taken from a creek with a sedimentation process as only pre-treatment. The cleaning performance was improved with ultrasound but after 3 weeks of operation damages occurred on the membranes. These effects were studied with online measurements of flux, trans-membrane-pressure and temperature, but also with integrity tests, turbidity measurements and visual examination.

Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude mice after irradiation with sub-threshold focused ultrasound for tumor ablation

PubMed Central

Wang, Rui; Guo, Qian; Chen, Yi Ni; Hu, Bing; Jiang, Li Xin

2017-01-01

We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were divided into three groups: Group A received sham irradiation, Group B received a moderate-acoustic energy dose (sub-threshold), and Group C received a high-acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and after irradiation. After irradiation, tumor growth was inhibited in Group B, and the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of contrast agent into and out of tumors before irradiation. After irradiation, CEUS revealed contrast agent perfusion only at the tumor periphery and irregular, un-perfused volumes of contrast agent within the tumors. DCE-US perfusion parameters, including peak intensity (PI) and area under the curve (AUC), had decreased 24 hours after irradiation. PI and AUC were increased 48 hours and 2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS is thus an effective method for early evaluation after irradiation with sub-threshold FUS. PMID:28402267

Hadamard-Encoded Multipulses for Contrast-Enhanced Ultrasound Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2017-11-01

The development of contrast-enhanced ultrasound (CEUS) imaging offers great opportunities for new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, the contrast agents (i.e., microbubbles) are utilized to improve the contrast between blood and tissue based on their high nonlinearity under low ultrasound pressure. In this paper, we propose a new CEUS pulse sequence by combining Hadamard-encoded multipulses (HEM) with fundamental frequency bandpass filter (i.e., filter centered on transmit frequency). HEM consecutively emits multipulses encoded by a second-order Hadamard matrix in each of the two transmission events (i.e., pulse-echo events), as opposed to conventional CEUS methods which emit individual pulses in two separate transmission events (i.e., pulse inversion (PI), amplitude modulation (AM), and PIAM). In HEM imaging, the microbubble responses can be improved by the longer transmit pulse, and the tissue harmonics can be suppressed by the fundamental frequency filter, leading to significantly improved contrast-to-tissue ratio (CTR) and signal-to-noise ratio (SNR). In addition, the fast polarity change between consecutive coded pulse emissions excites strong nonlinear microbubble echoes, further enhancing the CEUS image quality. The spatial resolution of HEM image is compromised as compared to other microbubble imaging methods due to the longer transmit pulses and the lower imaging frequency (i.e., fundamental frequency). However, the resolution loss was shown to be negligible and could be offset by the significantly enhanced CTR, SNR, and penetration depth. These properties of HEM can potentially facilitate robust CEUS imaging for many clinical applications, especially for deep abdominal organs and heart.

Dynamic Contrast-Enhanced Ultrasound Identifies Microcirculatory Alterations in Sepsis-Induced Acute Kidney Injury.

PubMed

Lima, Alexandre; van Rooij, Tom; Ergin, Bulent; Sorelli, Michele; Ince, Yasin; Specht, Patricia A C; Mik, Egbert G; Bocchi, Leonardo; Kooiman, Klazina; de Jong, Nico; Ince, Can

2018-05-15

We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Prospective controlled animal experiment study. Hospital-affiliated animal research institution. Fifteen female pigs. The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. In our lipopolysaccharide model, with resuscitation targeted at blood pressure, the contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

Using Ultrasound to Enhance Medical Students' Femoral Vascular Physical Examination Skills.

PubMed

Ahn, Justin S; French, Andrew J; Thiessen, Molly E W; Browne, Vaughn; Deutchman, Mark; Guiton, Gretchen; Madigosky, Wendy; Kendall, John L

2015-10-01

To determine whether the addition of ultrasound to traditional physical examination instruction improves junior medical students' abilities to locate the femoral pulse. Initially, 150 second-year medical students were taught the femoral pulse examination using traditional bedside teaching on standardized patients and online didactic videos. Students were then randomized into 2 groups: group 1 received ultrasound training first and then completed the standardized examination; and group 2 performed the standardized examination first and then received ultrasound training. On the standardized patients, the femoral artery was marked with invisible ink before the sessions using ultrasound. Compared to these markers, students were then evaluated on the accuracy of femoral artery pulse palpation and the estimated location of the femoral vein. All students completed a self-assessment survey after the ultrasound sessions. Ultrasound training improved the students' ability to palpate the femoral pulse (P= .02). However, ultrasound did not facilitate correct estimation of the femoral vein's anatomic location (P = .09). Confidence levels in localizing the femoral artery and vein were equal between groups at baseline, and both increased after the ultrasound sessions. The addition of ultrasound teaching to traditional physical examination instruction enhanced medical student competency and confidence with the femoral vascular examination. However, understanding of anatomy may require emphasis on precourse didactic material, but further study is required. © 2015 by the American Institute of Ultrasound in Medicine.

Ultrasound-enhanced rt-PA thrombolysis in an ex vivo porcine carotid artery model.

PubMed

Hitchcock, Kathryn E; Ivancevich, Nikolas M; Haworth, Kevin J; Caudell Stamper, Danielle N; Vela, Deborah C; Sutton, Jonathan T; Pyne-Geithman, Gail J; Holland, Christy K

2011-08-01

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. Copyright © 2011. Published by Elsevier Inc.

Integration of Real-Time Intraoperative Contrast-Enhanced Ultrasound and Color Doppler Ultrasound in the Surgical Treatment of Spinal Cord Dural Arteriovenous Fistulas.

PubMed

Della Pepa, Giuseppe Maria; Sabatino, Giovanni; Sturiale, Carmelo Lucio; Marchese, Enrico; Puca, Alfredo; Olivi, Alessandro; Albanese, Alessio

2018-04-01

In the surgical treatment of spinal dural arteriovenous fistulas (DAVFs), intraoperative definition of anatomic characteristics of the DAVF and identification of the fistulous point is mandatory to effectively exclude the DAVF. Intraoperative ultrasound and contrast-enhanced ultrasound integrated with color Doppler ultrasound was applied in the surgical setting for a cervical DAVF to identify the fistulous point and evaluate correct occlusion of the fistula. Integration of intraoperative ultrasound and contrast-enhanced ultrasound is a simple, cost-effective technique that provides an opportunity for real-time dynamic visualization of DAVF vascular patterns, identification of the fistulous point, and assessment of correct exclusion. Compared with other intraoperative tools, such as indocyanine green videoangiography, it allows the surgeon to visualize hidden anatomic and vascular structures, minimizing surgical manipulation and guiding the surgeon during resection. Copyright © 2018 Elsevier Inc. All rights reserved.

Numerical Study on Focusing of Ultrasounds in Microbubble-enhanced HIFU

NASA Astrophysics Data System (ADS)

Matsumoto, Yoichiro; Okita, Kohei; Takagi, Shu

2011-11-01

The injection of microbubbles into the target tissue enhances tissue heating in High-Intensity Focused Ultrasound therapy, via inertial cavitation. The control of the inertial cavitation is required to achieve the efficient tissue ablation. Microbubbles between a transducer and a target disturb the ultrasound propagation depending on the conditions. A method to clear such microbubbles has been proposed by Kajiyama et al. [Physics Procedia 3 (2010) 305-314]. In the method, the irradiation of intense ultrasounds with a burst waveform fragmentize microbubbles in the pathways before the irradiation of ultrasounds for tissue heating. The vitro experiment using a gel containing microbubbles has showed that the method enables to heat the target correctly by controlling the microbubble distribution. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing microbubbles with considering the size and number density distributions in space. The numerical simulation shows that the movement of the heating region from the transducer side to the target by controlling the microbubble distributions. The numerical results elucidate well the experimental ones.

Bas-relief map using texture analysis with application to live enhancement of ultrasound images.

PubMed

Du, Huarui; Ma, Rui; Wang, Xiaoying; Zhang, Jue; Fang, Jing

2015-05-01

For ultrasound imaging, speckle is one of the most important factors in the degradation of contrast resolution because it masks meaningful texture and has the potential to interfere with diagnosis. It is expected that researchers would explore appropriate ways to reduce the speckle noise, to find the edges of structures and enhance weak borders between different organs in ultrasound imaging. Inspired by the principle of differential interference contrast microscopy, a "bas-relief map" is proposed that depicts the texture structure of ultrasound images. Based on a bas-relief map, an adaptive bas-relief filter was developed for ultrafast despeckling. Subsequently, an edge map was introduced to enhance the edges of images in real time. The holistic bas-relief map approach has been used experimentally with synthetic phantoms and digital ultrasound B-scan images of liver, kidney and gallbladder. Based on the visual inspection and the performance metrics of the despeckled images, it was found that the bas-relief map approach is capable of effectively reducing the speckle while significantly enhancing contrast and tissue boundaries for ultrasonic images, and its speckle reduction ability is comparable to that of Kuan, Lee and Frost filters. Meanwhile, the proposed technique could preserve more intra-region details compared with the popular speckle reducing anisotropic diffusion technique and more effectively enhance edges. In addition, the adaptive bas-relief filter was much less time consuming than the Kuan, Lee and Frost filter and speckle reducing anisotropic diffusion techniques. The bas-relief map strategy is effective for speckle reduction and live enhancement of ultrasound images, and can provide a valuable tool for clinical diagnosis. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects

PubMed Central

Roberts, Victoria HJ; Lo, Jamie O; Salati, Jennifer A; Lewandowski, Katherine S; Lindner, Jonathan R; Morgan, Terry K; Frias, Antonio E

2016-01-01

Background The utero-placental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. Objective Here we demonstrate the feasibility of utilizing contrast-enhanced ultrasound to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. Study design Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n=6/group). Human subjects were recruited immediately prior to scheduled first trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition using a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. Results In macaques, rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and HSP70 as markers of apoptosis, nitrative and oxidative stress respectively were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11wks gestation and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast following first trimester ultrasound studies. Conclusions Use of contrast-enhanced ultrasound did not result in placental structural damage, and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound may offer a safe clinical tool for the identification of

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

PubMed Central

Nicolau, C; Bunesch, L; Peri, L; Salvador, R; Corral, J M; Mallofre, C; Sebastia, C

2011-01-01

Objective To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound. Methods 43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis. Results CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm. Conclusion CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies. PMID:21123306

Advanced ultrasound applications in the assessment of renal transplants: contrast-enhanced ultrasound, elastography, and B-flow.

PubMed

Morgan, Tara A; Jha, Priyanka; Poder, Liina; Weinstein, Stefanie

2018-04-09

Ultrasound is routinely used as the first imaging exam for evaluation of renal transplants and can identify most major surgical complications and evaluate vascularity with color Doppler. Ultrasound is limited, however, in the detection of parenchymal disease processes and Doppler evaluation is also prone to technical errors. Multiple new ultrasound applications have been developed and are under ongoing investigation which could add additional diagnostic capability to the routine ultrasound exam with minimal additional time, cost, and patient risk. Contrast-enhanced ultrasound (CEUS) can be used off-label in the transplant kidney, and can assist in detection of infection, trauma, and vascular complications. CEUS also can demonstrate perfusion of the transplant assessed quantitatively with generation of time-intensity curves. Future directions of CEUS include monitoring treatment response and microbubble targeted medication delivery. Elastography is an ultrasound application that can detect changes in tissue elasticity, which is useful to diagnose diffuse parenchymal disease, such as fibrosis, otherwise unrecognizable with ultrasound. Elastography has been successfully applied in other organs including the liver, thyroid, and breast; however, it is still under development for use in the transplant kidney. Unique properties of the transplant kidney including its heterogeneity, anatomic location, and other technical factors present challenges in the development of reference standard measurements. Lastly, B-flow imaging is a flow application derived from B-mode. This application can show the true lumen size of a vessel which is useful to depict vascular anatomy and bypasses some of the pitfalls of color Doppler such as demonstration of slow flow.

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

PubMed Central

Gündel, Daniel; Allmeroth, Mareli; Reime, Sarah; Zentel, Rudolf; Thews, Oliver

2017-01-01

Background Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. Materials and methods Six different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models. The cellular uptake of fluorescence-labeled polymers was measured under hypoxic (pO2 ≈1.5 mmHg) and acidic (pH 6.6) conditions. By using specific inhibitors, different endocytotic routes (macropinocytosis and clathrin-mediated, dynamin-dependent, cholesterol-dependent endocytosis) were analyzed separately. Results The current results revealed that the polymer uptake depends on the molecular structure, molecular weight and tumor line used. In AT1 cells, the uptake of random copolymer was five times stronger than the homopolymer, whereas in Walker-256 cells, the uptake of all polymers was much stronger, but this was independent of the molecular structure and size. Acidosis increased the uptake of random copolymer in AT1 cells but reduced the intracellular accumulation of homopolymer and block copolymer. Hypoxia reduced the uptake of all polymers in Walker-256 cells. Hydrophilic polymers (homopolymer and block copolymer) were taken up by all endocytotic routes studied, whereas the more lipophilic random copolymer seemed to be taken up preferentially by cholesterol- and dynamin-dependent endocytosis. Conclusion The study indicates that numerous parameters of the polymer (structure, size) and of the tumor (perfusion, vascular permeability, pH, pO2) modulate drug delivery, which makes it difficult to select the appropriate polymer for the individual patient

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia.

PubMed

Gündel, Daniel; Allmeroth, Mareli; Reime, Sarah; Zentel, Rudolf; Thews, Oliver

2017-01-01

Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. Six different N -(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models. The cellular uptake of fluorescence-labeled polymers was measured under hypoxic (pO 2 ≈1.5 mmHg) and acidic (pH 6.6) conditions. By using specific inhibitors, different endocytotic routes (macropinocytosis and clathrin-mediated, dynamin-dependent, cholesterol-dependent endocytosis) were analyzed separately. The current results revealed that the polymer uptake depends on the molecular structure, molecular weight and tumor line used. In AT1 cells, the uptake of random copolymer was five times stronger than the homopolymer, whereas in Walker-256 cells, the uptake of all polymers was much stronger, but this was independent of the molecular structure and size. Acidosis increased the uptake of random copolymer in AT1 cells but reduced the intracellular accumulation of homopolymer and block copolymer. Hypoxia reduced the uptake of all polymers in Walker-256 cells. Hydrophilic polymers (homopolymer and block copolymer) were taken up by all endocytotic routes studied, whereas the more lipophilic random copolymer seemed to be taken up preferentially by cholesterol- and dynamin-dependent endocytosis. The study indicates that numerous parameters of the polymer (structure, size) and of the tumor (perfusion, vascular permeability, pH, pO 2 ) modulate drug delivery, which makes it difficult to select the appropriate polymer for the individual patient.

Transdermal delivery of lercanidipine hydrochloride: effect of chemical enhancers and ultrasound.

PubMed

Shetty, Pallavi K; Suthar, Neelam A; Menon, Jyothsna; Deshpande, Praful B; Avadhani, Kiran; Kulkarni, Raghavendra V; Mutalik, Srinivas

2013-08-01

The effects of permeation enhancers and sonophoresis on the transdermal permeation of lercanidipine hydrochloride (LRDP) across mouse skin were investigated. Parameters including drug solubility, partition coefficient, drug degradation and drug permeation in skin were determined. Tween-20, dimethyl formamide, propylene glycol, poly ethylene glycol (5% v/v) and different concentration of ethanol were used for permeation enhancement. Low frequency ultrasound was also applied in the presence and absence of permeation enhancers to assess its effect on augmenting the permeation of drug. All the permeation enhancers, except propylene glycol, increased the transdermal permeation of LRDP. Sonophoresis significantly increased the cumulative amount of LRDP permeating through the skin in comparison to passive diffusion. A synergistic effect was noted when sonophoresis was applied in presence of permeation enhancers. The results suggest that the formulation of LRDP with an appropriate penetration enhancer may be useful in the development of a therapeutic system to deliver LRDP across the skin for a prolonged period (i.e., 24 h). The application of ultrasound in association with permeation enhancers could further serve as non-oral and non-invasive drug delivery modality for the immediate therapeutic effect.

Ultrasound enhanced thrombolysis: Clinical evidence

NASA Astrophysics Data System (ADS)

Alexandrov, Andrei V.

2005-04-01

Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

Hemostatic Effects of Microbubble-Enhanced Low-Intensity Ultrasound in a Liver Avulsion Injury Model

PubMed Central

Feng, Guiying; Liu, Jianhua; Zhao, Xiaochen; Wei, Jinglu; Ou, Wencai; Xiao, Shuyi; Hu, Zhiwen; Wei, Hongqin; Liu, Zheng

2014-01-01

Objectives Microbubble-enhanced therapeutic ultrasound (MEUS) can block the blood flow in the organs. The aim of this study was to evaluate the hemostatic effect of microbubble-enhanced pulsed, low-intensity ultrasound in a New Zealand White rabbit model of avulsion trauma of the liver. The therapeutic ultrasound (TUS) transducer was operated with the frequency of 1.2 MHz and an acoustic pressure of 3.4 MPa. Microbubble-(MB) enhanced ultrasound (MEUS) (n = 6) was delivered to the distal part of the liver where the avulsion was created. Livers were treated by TUS only (n = 4) or MB only (n = 4) which served as controls. Bleeding rates were measured and contrast enhanced ultrasound (CEUS) was performed to assess the hemostatic effect, and liver hemoperfusion before and after treatment. Generally, bleeding rates decreased more than 10-fold after the treatment with MEUS compared with those of the control group (P<0.05). CEUS showed significant declines in perfusion. The peak intensity value and the area under the curve also decreased after insonation compared with those of the control group (P<0.05). Histological examination showed cloudy and swollen hepatocytes, dilated hepatic sinusoids, perisinusoidal spaces with erythrocyte accumulation in small blood vessels, obvious hemorrhage around portal areas and scattered necrosis in liver tissues within the insonation area of MEUS Group. In addition, necrosis was found in liver tissue 48 h after insonation. We conclude that MEUS might provide an effective hemostatic therapy for serious organ trauma such as liver avulsion injury. PMID:24788757

Laser-enhanced thermal effect of moderate intensity focused ultrasound on bio-tissues

NASA Astrophysics Data System (ADS)

Zhao, JinYu; Zhang, ShuYi; Shui, XiuJi; Fan, Li

2017-09-01

For avoiding extra-damage to healthy tissues surrounding the focal point during high intensity focused ultrasound (HIFU) treatment in medical therapy, to reduce the ultrasonic intensity outside the focal point is expected. Thus, the heating processes induced by moderate intensity focused ultrasound (MIFU) and enhanced by combined irradiation of laser pulses for bio-tissues are studied in details. For fresh bio-tissues, the enhanced thermal effects by pulsed laser combined with MIFU irradiation are observed experimentally. To explore the mechanisms of these effects, several tissue-mimicking materials composed of agar mixed with graphite powders are prepared and studied for comparison, but the laser-enhanced thermal effects in these mimicking materials are much less than that in the fresh bio-tissues. Therefore, it is suggested that the laser-enhanced thermal effects may be mainly attributed to bio-activities and related photo-bio-chemical effects of fresh tissues.

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

Contrast-enhanced intravascular ultrasound pulse sequences for bandwidth-limited transducers.

PubMed

Maresca, David; Renaud, Guillaume; van Soest, Gijs; Li, Xiang; Zhou, Qifa; Shung, K Kirk; de Jong, Nico; van der Steen, Antonius F W

2013-04-01

We demonstrate two methods for vasa vasorum imaging using contrast-enhanced intravascular ultrasound, which can be performed using commercial catheters. Plaque neovascularization was recognized as an independent marker of coronary artery plaque vulnerability. IVUS-based methods to image the microvessels available to date require high bandwidth (-6 dB relative frequency bandwidth >70%), which are not routinely available commercially. We explored the potential of ultraharmonic imaging and chirp reversal imaging for vasa vasorum imaging. In vitro recordings were performed on a tissue-mimicking phantom using a commercial ultrasound contrast agent and a transducer with a center frequency of 34 MHz and a -6 dB relative bandwidth of 56%. Acoustic peak pressures <500 kPa were used. A tissue-mimicking phantom with channels down to 200 μm in diameter was successfully imaged by the two contrast detection sequences while the smallest channel stayed invisible in conventional intravascular ultrasound images. Ultraharmonic imaging provided the best contrast agent detection. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Optical tomography of fluorophores in dense scattering media based on ultrasound-enhanced chemiluminescence

NASA Astrophysics Data System (ADS)

Kobayashi, Masaki; Kikuchi, Naoto; Sato, Akihiro

2015-01-01

This letter proposes and demonstrates ultrasound-combined optical imaging in dense scattering media. A peroxyoxalate chemiluminescence system that includes fluorophores to chemically excite the pigment is stimulated by ultrasound irradiation with power of less than 0.14 W/cm2. Using focused ultrasound, the chemiluminescence is selectively spatially enhanced, which leads to imaging of the pigment when embedded in a light-scattering medium via scanning of the focal point. The ultrasonically enhanced intensity of the chemiluminescence depends on the base intensity of the chemiluminescence without the applied ultrasound irradiation, which thereby enables quantitative determination of the fluorophore concentration. The authors demonstrate the potential of this method to resolve chemiluminescent targets in a dense scattering medium that is comparable to biological tissue. An image was acquired of a chemiluminescent target that included indocyanine green as the fluorophore embedded at a depth of 20 mm in an Intralipid-10% 200 ml/l solution scattering medium (the reduced scattering coefficient was estimated to be approximately 1.3 mm-1), indicating the potential for expansion of this technique for use in biological applications.

Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model.

PubMed

Hitchcock, Kathryn E; Caudell, Danielle N; Sutton, Jonathan T; Klegerman, Melvin E; Vela, Deborah; Pyne-Geithman, Gail J; Abruzzo, Todd; Cyr, Peppar E P; Geng, Yong-Jian; McPherson, David D; Holland, Christy K

2010-06-15

The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1-MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n=8) and wild-type (n=8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and sub-endothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasound-exposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery. Copyright (c) 2010 Elsevier B.V. All rights reserved.

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

PubMed Central

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

2017-01-01

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

PubMed

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

2017-03-13

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

Contrast-Enhanced Ultrasound as a New Investigative Tool in Diagnostic Imaging of Muscle Injuries-A Pilot Study Evaluating Conventional Ultrasound, CEUS, and Findings in MRI.

PubMed

Hotfiel, Thilo; Heiss, Rafael; Swoboda, Bernd; Kellermann, Marion; Gelse, Kolja; Grim, Casper; Strobel, Deike; Wildner, Dane

2018-07-01

To emphasize the diagnostic value of contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries with different degrees of severity by comparing findings to established imaging modalities such as conventional ultrasound and magnetic resonance imaging (MRI). Case series. Institutional study. Conventional ultrasound and CEUS were performed in the Department of Internal Medicine. Magnetic resonance imaging was carried out in the Department of Radiology within the Magnetom Avanto 1.5T and Magnetom Skyra fit 3T (Siemens Healthineers, Erlangen, Germany) and in the Institution of Imaging Diagnostics and Therapy (Magnetom Avanto 1.5T; Siemens, Erlangen, Germany). Fifteen patients who underwent an acute muscle injury were recruited. The appearance and detectable size of muscle injuries were compared between each imaging modality. The injuries were assessed by 3 independent observers and blinded between imaging modalities. All 15 injuries were identified on MRI and CEUS, whereas 10 injuries showed abnormalities in conventional ultrasound. The determination and measurement revealed significant differences between conventional ultrasound and CEUS depending on injury severity. Contrast-enhanced ultrasound revealed an impairment of microcirculation in grade I lesions (corresponding to intramuscular edema observed in MRI), which was not detectable using conventional ultrasound. Our results indicate that performing CEUS seems to be a sensitive additional diagnostic modality in the early assessment of muscle injuries. Our results highlight the advantages of CEUS in the imaging of low-grade lesions when compared with conventional ultrasound, as this was the more accurate modality for identifying intramuscular edema.

Optical tomography of fluorophores in dense scattering media based on ultrasound-enhanced chemiluminescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Masaki, E-mail: masaki@tohtech.ac.jp; Kikuchi, Naoto; Sato, Akihiro

This letter proposes and demonstrates ultrasound-combined optical imaging in dense scattering media. A peroxyoxalate chemiluminescence system that includes fluorophores to chemically excite the pigment is stimulated by ultrasound irradiation with power of less than 0.14 W/cm{sup 2}. Using focused ultrasound, the chemiluminescence is selectively spatially enhanced, which leads to imaging of the pigment when embedded in a light-scattering medium via scanning of the focal point. The ultrasonically enhanced intensity of the chemiluminescence depends on the base intensity of the chemiluminescence without the applied ultrasound irradiation, which thereby enables quantitative determination of the fluorophore concentration. The authors demonstrate the potential of thismore » method to resolve chemiluminescent targets in a dense scattering medium that is comparable to biological tissue. An image was acquired of a chemiluminescent target that included indocyanine green as the fluorophore embedded at a depth of 20 mm in an Intralipid-10% 200 ml/l solution scattering medium (the reduced scattering coefficient was estimated to be approximately 1.3 mm{sup −1}), indicating the potential for expansion of this technique for use in biological applications.« less

Cumulative phase delay imaging - A new contrast enhanced ultrasound modality

NASA Astrophysics Data System (ADS)

Demi, Libertario; van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo

2015-10-01

Recently, a new acoustic marker for ultrasound contrast agents (UCAs) has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental pressure wave field components is in fact observable for ultrasound propagating through UCAs. This phenomenon is absent in the case of tissue nonlinearity and is dependent on insonating pressure and frequency, UCA concentration, and propagation path length through UCAs. In this paper, ultrasound images based on this marker are presented. The ULA-OP research platform, in combination with a LA332 linear array probe (Esaote, Firenze Italy), were used to image a gelatin phantom containing a PVC plate (used as a reflector) and a cylindrical cavity measuring 7 mm in diameter (placed in between the observation point and the PVC plate). The cavity contained a 240 µL/L SonoVueO® UCA concentration. Two insonating frequencies (3 MHz and 2.5 MHz) were used to scan the gelatine phantom. A mechanical index MI = 0.07, measured in water at the cavity location with a HGL-0400 hydrophone (Onda, Sunnyvale, CA), was utilized. Processing the ultrasound signals backscattered from the plate, ultrasound images were generated in a tomographic fashion using the filtered back-projection method. As already observed in previous studies, significantly higher CPD values are measured when imaging at a frequency of 2.5 MHz, as compared to imaging at 3 MHz. In conclusion, these results confirm the applicability of the discussed CPD as a marker for contrast imaging. Comparison with standard contrast-enhanced ultrasound imaging modalities will be the focus of future work.

The role of contrast-enhanced ultrasound in imaging carotid arterial diseases.

PubMed

Clevert, Dirk A; Paprottka, Philipp; Sommer, Wieland H; Helck, Andreas; Reiser, Maximilian F; Zengel, Pamela

2013-06-01

The standard of care for the initial diagnosis of carotid artery bifurcation diseases is carotid duplex ultrasound. Carotid abnormalities or difficult examinations may represent a diagnostic challenge in patients with clinical symptoms as well as in the follow-up after carotid endarterectomy, carotid artery stenting or other interventions. A promising new method in the diagnosis and follow-up of pathologic carotid diseases is contrast-enhanced ultrasound (CEUS). In comparison with magnetic resonance imaging or computed tomography, the contrast agents used for CEUS remain within the vascular space and hence can be used to study vascular disease and could provide additional information on carotid arterial diseases. This review describes the current carotid duplex ultrasound examination and compares the pathologic findings with CEUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Diagnostic value of contrast-enhanced ultrasound in thyroid nodules with calcification.

PubMed

Jiang, Jue; Shang, Xu; Wang, Hua; Xu, Yong-Bo; Gao, Ya; Zhou, Qi

2015-03-01

The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification. Copyright © 2014. Published by Elsevier Taiwan.

Ultrasound-enhanced bioscouring of greige cotton: regression analysis of process factors

USDA-ARS?s Scientific Manuscript database

Ultrasound-enhanced bioscouring process factors for greige cotton fabric are examined using custom experimental design utilizing statistical principles. An equation is presented which predicts bioscouring performance based upon percent reflectance values obtained from UV-Vis measurements of rutheniu...

Ultrasound-enhanced delivery of doxorubicin/all-trans retinoic acid-loaded nanodiamonds into tumors.

PubMed

Li, Huanan; Zeng, Deping; Wang, Zhenyu; Fang, Liaoqiong; Li, Faqi; Wang, Zhibiao

2018-03-14

To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm 2 . Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. DOX-ATRA-NDs demonstrate great potential in clinical applications.

Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict Microvascular Invasion in Hepatocellular Carcinoma?

PubMed

Zhu, Wei; Qing, Xiachuan; Yan, Feng; Luo, Yan; Li, Yongzhong; Zhou, Xiang

2017-08-01

The objective of this study was to investigate use of the washout rate of hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative determination of the presence of microvascular invasion. The study included 271 patients who underwent liver resection for hepatocellular carcinoma between April 2008 and December 2012, and were examined with contrast-enhanced ultrasound before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout patterns were classified according to the start time of washout: rapid, portal, delayed and slow. Rapid washout, presence of two or more tumors and tumor size ≥5 cm were identified as independent pre-operative predictors of microvascular invasion on multivariate analysis. Recurrence rates for patients with none, one, two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In combination with tumor number and tumor size, contrast-enhanced ultrasound washout rate may have a role in identifying hepatocellular carcinoma patients with microvascular invasion. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Value of contrast-enhanced ultrasound in the differential diagnosis of gallbladder lesion

PubMed Central

Zhang, Hui-Ping; Bai, Min; Gu, Ji-Ying; He, Ying-Qian; Qiao, Xiao-Hui; Du, Lian-Fang

2018-01-01

AIM To describe contrast-enhanced ultrasound (CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as (1) benign, (2) probably benign, (3) probably malignant or (4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared. RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS (e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8% and 95.2%, respectively. These were significantly higher than conventional ultrasound (82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer. CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound. PMID:29456413

Ultrasound-enhanced bioscouring of greige cotton: regression analysis of process factors

USDA-ARS?s Scientific Manuscript database

Process factors of enzyme concentration, time, power and frequency were investigated for ultrasound-enhanced bioscouring of greige cotton. A fractional factorial experimental design and subsequent regression analysis of the process factors were employed to determine the significance of each factor a...

Enhancement of mass transfer by ultrasound: Application to adsorbent regeneration and food drying/dehydration.

PubMed

Yao, Ye

2016-07-01

The physical mechanisms of heat and mass transfer enhancement by ultrasound have been identified by people. Basically, the effect of 'cavitation' induced by ultrasound is the main reason for the enhancement of heat and mass transfer in a liquid environment, and the acoustic streaming and vibration are the main reasons for that in a gaseous environment. The adsorbent regeneration and food drying/dehydration are typical heat and mass transfer process, and the intensification of the two processes by ultrasound is of complete feasibility. This paper makes an overview on recent studies regarding applications of power ultrasound to adsorbent regeneration and food drying/dehydration. The concerned adsorbents include desiccant materials (typically like silica gel) for air dehumidification and other ones (typically active carbon and polymeric resin) for water treatment. The applications of ultrasound in the regeneration of these adsorbents have been proved to be energy saving. The concerned foods are mostly fruits and vegetables. Although the ultrasonic treatment may cause food degradation or nutrient loss, it can greatly reduce the food processing time and decrease drying temperature. From the literature, it can be seen that the ultrasonic conditions (i.e., acoustic frequency and power levels) are always focused on during the study of ultrasonic applications. The increasing number of relevant studies argues that ultrasound is a very promising technology applied to the adsorbent regeneration and food drying/dehydration. Copyright © 2016 Elsevier B.V. All rights reserved.

Cumulative phase delay imaging - A new contrast enhanced ultrasound modality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demi, Libertario, E-mail: l.demi@tue.nl; Sloun, Ruud J. G. van; Mischi, Massimo

Recently, a new acoustic marker for ultrasound contrast agents (UCAs) has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental pressure wave field components is in fact observable for ultrasound propagating through UCAs. This phenomenon is absent in the case of tissue nonlinearity and is dependent on insonating pressure and frequency, UCA concentration, and propagation path length through UCAs. In this paper, ultrasound images based on this marker are presented. The ULA-OP research platform, in combination with a LA332 linear array probe (Esaote, Firenze Italy), were used to image a gelatin phantom containing a PVC platemore » (used as a reflector) and a cylindrical cavity measuring 7 mm in diameter (placed in between the observation point and the PVC plate). The cavity contained a 240 µL/L SonoVueO{sup ®} UCA concentration. Two insonating frequencies (3 MHz and 2.5 MHz) were used to scan the gelatine phantom. A mechanical index MI = 0.07, measured in water at the cavity location with a HGL-0400 hydrophone (Onda, Sunnyvale, CA), was utilized. Processing the ultrasound signals backscattered from the plate, ultrasound images were generated in a tomographic fashion using the filtered back-projection method. As already observed in previous studies, significantly higher CPD values are measured when imaging at a frequency of 2.5 MHz, as compared to imaging at 3 MHz. In conclusion, these results confirm the applicability of the discussed CPD as a marker for contrast imaging. Comparison with standard contrast-enhanced ultrasound imaging modalities will be the focus of future work.« less

Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro.

PubMed

Ma, Jing; Shen, Ming; Xu, Chang Song; Sun, Ying; Duan, You Rong; Du, Lian Fang

2016-11-29

A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.

Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers.

PubMed

Bo, Xiao-Wan; Xu, Hui-Xiong; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

2016-11-01

To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging

Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers

PubMed Central

Bo, Xiao-Wan; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

2016-01-01

Objective: To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. Methods: 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. Results: On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Conclusion: Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in

Mechanistic insight into ultrasound induced enhancement of simultaneous saccharification and fermentation of Parthenium hysterophorus for ethanol production.

PubMed

Singh, Shuchi; Agarwal, Mayank; Sarma, Shyamali; Goyal, Arun; Moholkar, Vijayanand S

2015-09-01

This paper presents investigations into mechanism of ultrasound assisted bioethanol synthesis using Parthenium hysterophorus biomass through simultaneous saccharification and fermentation (SSF) mode. Approach of coupling experimental results to mathematical model for SSF using Genetic Algorithm based optimization has been adopted. Comparison of model parameters for experiments with mechanical shaking and sonication (10% duty cycle) give an interesting mechanistic account of influence of ultrasound on SSF system. A 4-fold rise in ethanol and cell mass productivity is seen with ultrasound. The analysis reveals following facets of influence of ultrasound on SSF: increase in Monod constant for glucose for cell growth, maximal specific growth rate and inhibition constant of cell growth by glucose and reduction in specific cell death rate. Values of inhibition constant of cell growth by ethanol (K3E), and constants for growth associated (a) and non-growth associated (b) ethanol production remained unaltered with sonication. Beneficial effects of ultrasound are attributed to enhanced cellulose hydrolysis, enhanced trans-membrane transport of substrate and products as well as dilution of the toxic substances due to micro-convection induced by ultrasound. Intrinsic physiological functioning of cells remained unaffected by ultrasound as indicated by unaltered values of K3E, a and b. Copyright © 2015 Elsevier B.V. All rights reserved.

[Application of CO2 enhanced ultrasound for two-stage operation of hepatic tumors].

PubMed

Wang, W; Xu, Z; Fan, J

1996-12-01

The feasibility of CO2 enhanced ultrasound (CO2-EUS) was evaluated in two-stage operation patients with hepatic tumors. CO2-EUS was carried out in nine patients with indwelling catheter within hepatic artery for two-stage operation of liver cancer. CO2 microbubbles mixing by 5 ml of 5% NaHCO3 and 2.5 ml of 5% Vitamine C were injected into the indwelling catheter. The computed sonography of ACUSON 128XP/10 with a 3.5 MHz convex transducer was used for this study. The enhanced parenchyma of the liver obtained by CO2-EUS and the lasting time of enhancement was about 8 minutes. The hepatic tumors, after chemotherapeutic treatment via indwelling catheter, were variously enhanced by CO2 microbubbles. The enhanced sonogram of the tumors took the forms of hypoechoic, ring-like, or spotty enhanced pattern lasting for more than 30 minutes. The margin of the enhanced tumors was very clear in CO2-EUS. CO2-EUS detected five more lesions (size 1-3 cm) besides 9 lesions by conventional ultrasound. CO2-EUS was extremely useful in evaluating curative effects of tumor, increasing detection rates of small tumor, and improving thoroughness of two-stage operation.

[Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase].

PubMed

Hotfiel, T; Carl, H D; Swoboda, B; Engelhardt, M; Heinrich, M; Strobel, D; Wildner, D

2016-03-01

Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue(®), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was

Ultrasound-enhanced delivery of antibiotics and anti-inflammatory drugs into the eye.

PubMed

Nabili, Marjan; Patel, Hetal; Mahesh, Sankaranarayana P; Liu, Ji; Geist, Craig; Zderic, Vesna

2013-04-01

Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3-1.0 W/cm(2) and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%-126% and 32%-109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p < 0.05) achieved at all treatment parameter combinations (compared with sham treatments) except for 1-MHz ultrasound applications for dexamethasone experiments. This permeability increase was highest at 400 kHz and appeared to be higher at higher intensities applied. Histologic analysis showed structural changes that were limited to epithelial layers of cornea. In summary, ultrasound application provided enhancement of drug delivery, increasing the permeability of the cornea for the anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

PubMed

Timor-Tritsch, Ilan E; Haynes, Meagan Campol; Monteagudo, Ana; Khatib, Nizar; Kovács, Sándor

2016-06-01

Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular

Ultrasound Enhanced Matrix Metalloproteinase-9 Triggered Release of Contents from Echogenic Liposomes

PubMed Central

Nahire, Rahul; Paul, Shirshendu; Scott, Michael D.; Singh, Raushan K.; Muhonen, Wallace W.; Shabb, John; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2012-01-01

The extracellular enzyme matrix metalloproteinase-9 (MMP-9) is overexpressed in atherosclerotic plaques and in metastatic cancers. The enzyme is responsible for rupture of the plaques and for the invasion and metastasis of a large number of cancers. The ability of ultrasonic excitation to induce thermal and mechanical effects has been used to release drugs from different carriers. However, majority of these studies were performed with low frequency ultrasound (LFUS) at kHz frequencies. Clinical usage of LFUS excitations will be limited due to harmful biological effects. Herein, we report our results on the release of encapsulated contents from substrate lipopeptide incorporated echogenic liposomes triggered by recombinant human MMP-9. The contents release was further enhanced by the application of diagnostic frequency (3 MHz) ultrasound. The echogenic liposomes were successfully imaged employing a medical ultrasound transducer (4 – 15 MHz). The conditioned cell culture media from cancer cells (secreting MMP-9) released the encapsulated dye from the liposomes (30 – 50%) and this release is also increased (50 – 80%) by applying diagnostic frequency ultrasound (3 MHz) for 3 minutes. With further developments, these liposomes have the potential to serve as multimodal carriers for triggered release and simultaneous ultrasound imaging. PMID:22849291

Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models.

PubMed

Wong, Andrew W; Fite, Brett Z; Liu, Yu; Kheirolomoom, Azadeh; Seo, Jai W; Watson, Katherine D; Mahakian, Lisa M; Tam, Sarah M; Zhang, Hua; Foiret, Josquin; Borowsky, Alexander D; Ferrara, Katherine W

2016-01-01

Magnetic resonance-guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma-bearing FVB/n and BALB/c mice. We observed a 5-fold and 50-fold enhancement of liposome and drug concentration, respectively, within MRgFUS thermal ablation-treated tumors along with dense accumulation within the surrounding tissue rim. Ultrasound-enhanced drug accumulation was rapid and durable and greatly increased total tumor drug exposure over time. In addition, we found that the small molecule gadoteridol accumulates around and within ablated tissue. We further demonstrated that dilated vasculature, loss of vascular integrity resulting in extravasation of blood cells, stromal inflammation, and loss of cell-cell adhesion and tissue architecture all contribute to the enhanced accumulation of the liposomes and small molecule probe. The locally enhanced liposome accumulation was preserved even after a multiweek protocol of doxorubicin-loaded liposomes and partial ablation. Finally, by supplementing ablation with concurrent liposomal drug therapy, a complete and durable response was obtained using protocols for which a sub-mm rim of tumor remained after ablation.

Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models

PubMed Central

Wong, Andrew W.; Fite, Brett Z.; Liu, Yu; Kheirolomoom, Azadeh; Seo, Jai W.; Watson, Katherine D.; Mahakian, Lisa M.; Tam, Sarah M.; Zhang, Hua; Foiret, Josquin; Borowsky, Alexander D.; Ferrara, Katherine W.

2015-01-01

Magnetic resonance–guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma–bearing FVB/n and BALB/c mice. We observed a 5-fold and 50-fold enhancement of liposome and drug concentration, respectively, within MRgFUS thermal ablation–treated tumors along with dense accumulation within the surrounding tissue rim. Ultrasound-enhanced drug accumulation was rapid and durable and greatly increased total tumor drug exposure over time. In addition, we found that the small molecule gadoteridol accumulates around and within ablated tissue. We further demonstrated that dilated vasculature, loss of vascular integrity resulting in extravasation of blood cells, stromal inflammation, and loss of cell-cell adhesion and tissue architecture all contribute to the enhanced accumulation of the liposomes and small molecule probe. The locally enhanced liposome accumulation was preserved even after a multiweek protocol of doxorubicin-loaded liposomes and partial ablation. Finally, by supplementing ablation with concurrent liposomal drug therapy, a complete and durable response was obtained using protocols for which a sub-mm rim of tumor remained after ablation. PMID:26595815

Electrolytic echo enhancement: a novel method to make needles more reflective to ultrasound.

PubMed

Cockburn, John F; Khosh, Stefan K

2014-04-01

This study examines the effect of augmenting the ultrasound reflectivity of needles using a novel electrolytic echo enhancement method. Needles were connected by a lead to the negative terminal of a 4.5 V direct current source. A grounding pad, connected to the positive terminal, was positioned on the undersurface of an ex vivo ox liver phantom. During needle insertion into the liver, electrolysis was induced creating a layer of gas on the needle electrode. Analysis of images showed a significant increase in needle brightness using electrolytic echo enhancement. Brightness was found to increase by a factor of ×3.6 compared with controls (P < 0.001). Electrolytic echo enhancement has the potential to make ultrasound-guided procedures safer and quicker for patients and increase the confidence of operators in their ability to see the whole needle including its tip. © 2014 The Royal Australian and New Zealand College of Radiologists.

Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent.

PubMed

Datta, Saurabh; Coussios, Constantin-C; Ammi, Azzdine Y; Mast, T Douglas; de Courten-Myers, Gabrielle M; Holland, Christy K

2008-09-01

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity, was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity. A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 microm) and plasminogen (241 microm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

Ultrasound-enhanced nanotherapy of pancreatic cancer

NASA Astrophysics Data System (ADS)

Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

2010-03-01

The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

Optically generated ultrasound for enhanced drug delivery

DOEpatents

Visuri, Steven R.; Campbell, Heather L.; Da Silva, Luiz

2002-01-01

High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

Ultrasound beam steering of oxygen nanobubbles for enhanced bladder cancer therapy.

PubMed

Bhandari, Pushpak; Novikova, Gloriia; Goergen, Craig J; Irudayaraj, Joseph

2018-02-15

New intravesical treatment approaches for bladder cancer are needed as currently approved treatments show several side effects and high tumor recurrence rate. Our study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated cellulosic nanobubbles as a novel agent for imaging and ultrasound guided drug delivery. In this study, we show that oxygen nanobubbles (ONB) can be propelled (up to 40 mm/s) and precisely guided in vivo to the tumor by an ultrasound beam. Nanobubble velocity can be controlled by altering the power of the ultrasound Doppler beam, while nanobubble direction can be adjusted to different desired angles by altering the angle of the beam. Precise ultrasound beam steering of oxygen nanobubbles was shown to enhance the efficacy of mitomycin-C, resulting in significantly lower tumor progression rates while using a 50% lower concentration of chemotherapeutic drug. Further, dark field imaging was utilized to visualize and quantify the ONB ex vivo. ONBs were found to localize up to 500 µm inside the tumor using beam steering. These results demonstrate the potential of an oxygen nanobubble drug encapsulated system to become a promising strategy for targeted drug delivery because of its multimodal (imaging and oxygen delivery) and multifunctional (targeting and hypoxia programming) properties.

Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors.

PubMed

Yang, Qian; Tang, Peng; He, Guangbin; Ge, Shuping; Liu, Liwen; Zhou, Xiaodong

2017-08-01

We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Contrast-enhanced ultrasound in portal venous system aneurysms: a multi-center study.

PubMed

Tana, Claudio; Dietrich, Christoph F; Badea, Radu; Chiorean, Liliana; Carrieri, Vincenzo; Schiavone, Cosima

2014-12-28

To investigate contrast-enhanced ultrasound (CEUS) findings in portal venous system aneurysms (PVSAs). In this multi-center, retrospective, case series study, we evaluated CEUS features of seven cases of PVSAs that were found incidentally on conventional ultrasound in the period 2007-2013. Three Ultrasound Centers were involved (Chieti, Italy, Bad Mergentheim, Germany, and Cluj-Napoca, Romania). All patients underwent CEUS with Sonovue(®) (Bracco, Milan, Italy) at a standard dose of 2.4 mL, followed by 10 mL of 0.9% saline solution. The examinations were performed using multifrequency transducers and low mechanical index. We considered aneurysmal a focal dilatation of the portal venous system with a size that was significantly greater than the remaining segments of the same vein, and that was equal or larger than 21 mm for the extrahepatic segments of portal venous system, main portal vein and bifurcation, and 9 mm for the intrahepatic branches. After contrast agent injection, all PVSAs were not enhanced in the arterial phase (starting 8-22 s). All PVSAs were then rapidly enhanced in the early portal venous phase (starting three to five seconds after the arterial phase, 11-30 s), with persistence and slow washout of the contrast agent in the late phase (starting 120 s). In all patients, CEUS confirmed the presence of a "to-and-fro" flow by showing a swirling pattern within the dilatation in the early portal venous phase. CEUS also improved the delineation of the lumen, and was reliable in showing its patency degree and integrity of walls. In one patient, CEUS showed a partial enhancement of the lumen with a uniformly nonenhancing area in the portal venous and late phases, suggesting thrombosis. In our case series, we found that CEUS could be useful in the assessment and follow-up of a PVSA. Further studies are needed to validate its diagnostic accuracy.

Ultrasound enhanced process for extracting metal species in supercritical fluids

DOEpatents

Wai, Chien M.; Enokida, Youichi

2006-10-31

Improved methods for the extraction or dissolution of metals, metalloids or their oxides, especially lanthanides, actinides, uranium or their oxides, into supercritical solvents containing an extractant are disclosed. The disclosed embodiments specifically include enhancing the extraction or dissolution efficiency with ultrasound. The present methods allow the direct, efficient dissolution of UO₂ or other uranium oxides without generating any waste stream or by-products.

Effect of modulated ultrasound parameters on ultrasound-induced thrombolysis.

PubMed

Soltani, Azita; Volz, Kim R; Hansmann, Doulas R

2008-12-07

The potential of ultrasound to enhance enzyme-mediated thrombolysis by application of constant operating parameters (COP) has been widely demonstrated. In this study, the effect of ultrasound with modulated operating parameters (MOP) on enzyme-mediated thrombolysis was investigated. The MOP protocol was applied to an in vitro model of thrombolysis. The results were compared to a COP with the equivalent soft tissue thermal index (TIS) over the duration of ultrasound exposure of 30 min (p < 0.14). To explore potential differences in the mechanism responsible for ultrasound-induced thrombolysis, a perfusion model was used to measure changes in average fibrin pore size of clot before, after and during exposure to MOP and COP protocols and cavitational activity was monitored in real time for both protocols using a passive cavitation detection system. The relative lysis enhancement by each COP and MOP protocol compared to alteplase alone yielded values of 33.69 +/- 12.09% and 63.89 +/- 15.02% in a thrombolysis model, respectively (p < 0.007). Both COP and MOP protocols caused an equivalent significant increase in average clot pore size of 2.09 x 10(-2) +/- 0.01 microm and 1.99 x 10(-2) +/- 0.004 microm, respectively (p < 0.74). No signatures of inertial or stable cavitation were observed for either acoustic protocol. In conclusion, due to mechanisms other than cavitation, application of ultrasound with modulated operating parameters has the potential to significantly enhance the relative lysis enhancement compared to application of ultrasound with constant operating parameters.

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

PubMed

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Toward a real-time system for temporal enhanced ultrasound-guided prostate biopsy.

PubMed

Azizi, Shekoofeh; Van Woudenberg, Nathan; Sojoudi, Samira; Li, Ming; Xu, Sheng; Abu Anas, Emran M; Yan, Pingkun; Tahmasebi, Amir; Kwak, Jin Tae; Turkbey, Baris; Choyke, Peter; Pinto, Peter; Wood, Bradford; Mousavi, Parvin; Abolmaesumi, Purang

2018-03-27

We have previously proposed temporal enhanced ultrasound (TeUS) as a new paradigm for tissue characterization. TeUS is based on analyzing a sequence of ultrasound data with deep learning and has been demonstrated to be successful for detection of cancer in ultrasound-guided prostate biopsy. Our aim is to enable the dissemination of this technology to the community for large-scale clinical validation. In this paper, we present a unified software framework demonstrating near-real-time analysis of ultrasound data stream using a deep learning solution. The system integrates ultrasound imaging hardware, visualization and a deep learning back-end to build an accessible, flexible and robust platform. A client-server approach is used in order to run computationally expensive algorithms in parallel. We demonstrate the efficacy of the framework using two applications as case studies. First, we show that prostate cancer detection using near-real-time analysis of RF and B-mode TeUS data and deep learning is feasible. Second, we present real-time segmentation of ultrasound prostate data using an integrated deep learning solution. The system is evaluated for cancer detection accuracy on ultrasound data obtained from a large clinical study with 255 biopsy cores from 157 subjects. It is further assessed with an independent dataset with 21 biopsy targets from six subjects. In the first study, we achieve area under the curve, sensitivity, specificity and accuracy of 0.94, 0.77, 0.94 and 0.92, respectively, for the detection of prostate cancer. In the second study, we achieve an AUC of 0.85. Our results suggest that TeUS-guided biopsy can be potentially effective for the detection of prostate cancer.

Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

Renaud, G.; Bosch, J. G.; ten Kate, G. L.; Shamdasani, V.; Entrekin, R.; de Jong, N.; van der Steen, A. F. W.

2012-11-01

Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image.

Relapses in three patients with Takayasu arteritis under tocilizumab treatment detected by contrast enhanced ultrasound.

PubMed

Czihal, Michael; Lottspeich, Christian; Schröttle, Angelika; Treitl, Karla Maria; Treitl, Marcus; Leipe, Jan; Schulze-Koops, Hendrik; Hoffmann, Ulrich; Dechant, Claudia

2018-02-01

Takayasu arteritis (TA) is a rare large vessel vasculitis, affecting the aorta and its major branches, typically in young women. In this case report, we present three cases of young women of Caucasian descent who experienced relapses while under treatment with the monoclonal humanized antibody to the interleukin 6 receptor, tocilizumab. Active vasculitic lesions of the supraaortic (common carotid and axillary) arteries were detected and characterized via high resolution contrast enhanced ultrasound. Based on these cases, we discuss the potential role of contrast enhanced ultrasound in the diagnosis and follow-up of TA as well as the current data on the efficacy of tocilizumab in the treatment of TA.

Iodine-enhanced ultrasound degradation of sulfamethazine in water.

PubMed

Yang, Xiao-Yu; Wei, Hong; Li, Ke-Bin; He, Qiang; Xie, Jian-Cang; Zhang, Jia-Tong

2018-04-01

This study investigated sulfamethazine (SMT) ultrasound degradation, enhanced by iodine radicals, generated by potassium iodide (KI) and hydrogen peroxide (H 2 O 2 ) in situ. The results showed that the ultrasound/H 2 O 2 /KI (US/H 2 O 2 /KI) combination treatment achieved an 85.10 ± 0.45% SMT removal (%) in 60 min under the following conditions: pH = 3.2, ultrasound power of 195 W, initial SMT concentration of 0.04 mmol·L -1 , H 2 O 2 concentration of 120 mmol·L -1 , and KI concentration of 2.4 mmol·L -1 . UV-Vis spectrophotometric monitoring of molecular iodine (I 2 ) and triiodide (I 3 - ) revealed a correlation between the SMT degradation and the iodine change in the solution. Quenching experiments using methanol, t-butanol and thiamazole as radical scavengers indicated that iodine radicals, such as I and I 2 - , were more important than hydroxyl radicals (HO) for SMT degradation. SMT degradation under the US/H 2 O 2 /KI treatment followed pseudo-first order reaction kinetics. The activation energy (E a ) of SMT degradation was 7.75 ± 0.61 kJ·mol -1 , which suggested the reaction was controlled by the diffusion step. Moreover, TOC removal was monitored, and the obtained results revealed that it was not as effective as SMT degradation under the US/H 2 O 2 /KI system. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrasound-Enhanced Delivery of Antibiotics and Anti-Inflammatory Drugs into the Eye

PubMed Central

Nabili, Marjan; Patel, Hetal; Mahesh, Sankaranarayana P.; Liu, Ji; Geist, Craig; Zderic, Vesna

2013-01-01

Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3–1.0 W/cm2 and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%–126% and 32%–109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p < 0.05) achieved at all treatment parameter combinations (compared with sham treatments) except for 1-MHz ultrasound applications for dexamethasone experiments. This permeability increase was highest at 400 kHz and appeared to be higher at higher intensities applied. Histologic analysis showed structural changes that were limited to epithelial layers of cornea. In summary, ultrasound application provided enhancement of drug delivery, increasing the permeability of the cornea for the anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. (E-mail: mnabili@gwu.edu) PMID:23415283

Delay and Standard Deviation Beamforming to Enhance Specular Reflections in Ultrasound Imaging.

PubMed

Bandaru, Raja Sekhar; Sornes, Anders Rasmus; Hermans, Jeroen; Samset, Eigil; D'hooge, Jan

2016-12-01

Although interventional devices, such as needles, guide wires, and catheters, are best visualized by X-ray, real-time volumetric echography could offer an attractive alternative as it avoids ionizing radiation; it provides good soft tissue contrast, and it is mobile and relatively cheap. Unfortunately, as echography is traditionally used to image soft tissue and blood flow, the appearance of interventional devices in conventional ultrasound images remains relatively poor, which is a major obstacle toward ultrasound-guided interventions. The objective of this paper was therefore to enhance the appearance of interventional devices in ultrasound images. Thereto, a modified ultrasound beamforming process using conventional-focused transmit beams is proposed that exploits the properties of received signals containing specular reflections (as arising from these devices). This new beamforming approach referred to as delay and standard deviation beamforming (DASD) was quantitatively tested using simulated as well as experimental data using a linear array transducer. Furthermore, the influence of different imaging settings (i.e., transmit focus, imaging depth, and scan angle) on the obtained image contrast was evaluated. The study showed that the image contrast of specular regions improved by 5-30 dB using DASD beamforming compared with traditional delay and sum (DAS) beamforming. The highest gain in contrast was observed when the interventional device was tilted away from being orthogonal to the transmit beam, which is a major limitation in standard DAS imaging. As such, the proposed beamforming methodology can offer an improved visualization of interventional devices in the ultrasound image with potential implications for ultrasound-guided interventions.

Acoustically active liposome-nanobubble complexes for enhanced ultrasonic imaging and ultrasound-triggered drug delivery.

PubMed

Nguyen, An T; Wrenn, Steven P

2014-01-01

Ultrasound is well known as a safe, reliable imaging modality. A historical limitation of ultrasound, however, was its inability to resolve structures at length scales less than nominally 20 µm, which meant that classical ultrasound could not be used in applications such as echocardiography and angiogenesis where one requires the ability to image small blood vessels. The advent of ultrasound contrast agents, or microbubbles, removed this limitation and ushered in a new wave of enhanced ultrasound applications. In recent years, the microbubbles have been designed to achieve yet another application, namely ultrasound-triggered drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic' vehicles, meaning they can do both therapy (drug delivery) and imaging (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles, however, is perhaps less than ideal when compared to traditional drug delivery vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug carrying capacities. The drawback of the traditional drug delivery vehicles is that they are not naturally acoustically active and cannot be used for imaging. The notion of a theranostic vehicle is sufficiently intriguing that many attempts have been made in recent years to achieve a vehicle that combines the echogenicity of microbubbles with the drug carrying capacity of liposomes. The attempts can be classified into three categories, namely entrapping, tethering, and nesting. Of these, nesting is the newest-and perhaps the most promising. © 2014 Wiley Periodicals, Inc.

Enhancing laser thermal-therapy using ultrasound-microbubbles and gold nanorods: In vitro investigation

NASA Astrophysics Data System (ADS)

Tarapacki, Christine; Kumaradas, Carl; Karshafian, Raffi

2012-11-01

Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption, leading to a local temperature increase and causing irreversible cell damage. One of the key challenges in using GNR as a thermal therapy agent is to deliver a concentration of GNR to generate sufficient heat and cause cell death. In this study, ultrasound and microbubble induced sonoporation is used to enhance intracellular uptake of GNR and improve the therapeutic outcome of laserinduced thermal therapy. Acute myeloid leukemia (AML) cells in suspension (0.6 mL) were treated with ultrasound and microbubbles (USMB) at 1 MHz frequency, 16 microseconds pulse duration, 1 kHz pulse repetition frequency, 1 minute insonation time, varying acoustic pressures (0, 1.26 and 1.73 MPa) and 10 μL Definity microbubble agent with and without GNR (12 nm × 48 nm) at varying concentration (1.0×1010 to 2.5×1011 GNR/mL). The GNR were manufactured through wet chemical synthesis process and measured using Transmission Electron Microscopy (TEM) and Atomic Absorption Spectroscopy (AAS) for size and concentration respectively. Following ultrasound and microbubble treatment, cells were centrifuged to remove excess gold nanorods and treated in suspension with an 810 nm laser (Diomed 60 NIR) at 4 W for 5 minutes. A thermal camera (FLIR Thermovision A40) was positioned to monitor the sample temperature throughout laser treatment and cell viability was assessed using flow cytometry with propidium iodide. Cell viability of 18±2% was achieved with GNR+USMB (1.26 MPa) compared to 72±3% with GNR alone (12 hour incubation) and 99±0.2% with USMB (1.26 MPa) alone. With increasing GNR concentration during ultrasound and microbubble treatment, laser induced sample temperature increased and consequently cell viability decreased. Cell viability decreased from 92±1% at 1.0×1011 GNR/mL to 29±5% at 1.5×1011 GNR/mL concentration with corresponding maximum temperatures of 50°C and 54°C, respectively

Application of imaging fusion combining contrast-enhanced ultrasound and magnetic resonance imaging in detection of hepatic cellular carcinomas undetectable by conventional ultrasound.

PubMed

Dong, Yi; Wang, Wen-Ping; Mao, Feng; Ji, Zheng-Biao; Huang, Bei-Jian

2016-04-01

The aim of this study is to explore the value of volume navigation image fusion-assisted contrast-enhanced ultrasound (CEUS) in detection for radiofrequency ablation guidance of hepatocellular carcinomas (HCCs), which were undetectable on conventional ultrasound. From May 2012 to May 2014, 41 patients with 49 HCCs were included in this study. All lesions were detected by dynamic magnetic resonance imaging (MRI) and planned for radiofrequency ablation but were undetectable on conventional ultrasound. After a bolus injection of 2.4 ml SonoVue® (Bracco, Italy), LOGIQ E9 ultrasound system with volume navigation system (version R1.0.5, GE Healthcare, Milwaukee, WI, USA) was used to fuse CEUS and MRI images. The fusion time, fusion success rate, lesion enhancement pattern, and detection rate were analyzed. Image fusions were conducted successfully in 49 HCCs, the technical success rate was 100%. The average fusion time was (9.2 ± 2.1) min (6-12 min). The mean diameter of HCCs was 25.2 ± 5.3 mm (mean ± SD), and mean depth was 41.8 ± 17.2 mm. The detection rate of HCCs using CEUS/MRI imaging fusion (95.9%, 47/49) was significantly higher than CEUS (42.9%, 21/49) (P < 0.05). For small HCCs (diameter, 1-2 cm), the detection rate using imaging fusion (96.9%, 32/33) was also significantly higher than CEUS (18.2%, 6/33) (P < 0.01). All HCCs displayed a rapid wash-in pattern in the arterial phase of CEUS. Imaging fusion combining CEUS and MRI is a promising technique to improve the detection, precise localization, and accurate diagnosis of undetectable HCCs on conventional ultrasound, especially small and atypical HCCs. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Detection of vascularity in wrist tenosynovitis: power doppler ultrasound compared with contrast-enhanced grey-scale ultrasound.

PubMed

Klauser, Andrea S; Franz, Magdalena; Arora, Rohit; Feuchtner, Gudrun M; Gruber, Johann; Schirmer, Michael; Jaschke, Werner R; Gabl, Markus F

2010-01-01

We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ± 11.8 years) with a clinical diagnosis of tenosynovitis were examined with B-mode ultrasonography, PDUS, and CEUS by using a second-generation contrast agent, SonoVue (Bracco Diagnostics, Milan, Italy) and a low-mechanical-index ultrasound technique. Thickness of synovitis, extent of vascularized pannus, intensity of peritendinous vascularisation, and detection of intratendinous vessels was incorporated in a 3-score grading system (grade 0 to 2). Interobserver variability was calculated. With CEUS, a significantly greater extent of vascularity could be detected than by using PDUS (P < 0.001). In terms of peri- and intratendinous vessels, CEUS was significantly more sensitive in the detection of vascularization compared with PDUS (P < 0.001). No significant correlation between synovial thickening and extent of vascularity could be found (P = 0.089 to 0.097). Interobserver reliability was calculated to be excellent when evaluating the grading score (κ = 0.811 to 1.00). CEUS is a promising tool to detect tendon vascularity with higher sensitivity than PDUS by improved detection of intra- and peritendinous vascularity.

The ultrasound-enhanced bioscouring performance of four polygalacturonase enzymes obtained from rhizopus oryzae

USDA-ARS?s Scientific Manuscript database

An analytical and statistical method has been developed to measure the ultrasound-enhanced bioscouring performance of milligram quantities of endo- and exo-polygalacturonase enzymes obtained from Rhizopus oryzae fungi. UV-Vis spectrophotometric data and a general linear mixed models procedure indic...

Acoustic Droplet Vaporization for the Enhancement of Ultrasound Thermal Therapy.

PubMed

Zhang, Man; Fabiilli, Mario; Carson, Paul; Padilla, Frederic; Swanson, Scott; Kripfgans, Oliver; Fowlkes, Brian

2010-10-11

Acoustic droplet vaporization (ADV) is an ultrasound method for converting biocompatible microdroplets into microbubbles. The objective is to demonstrate that ADV bubbles can enhance high intensity focused ultrasound (HIFU) therapy by controlling and increasing energy absorption at the focus. Thermal phantoms were made with or without droplets. Compound lesions were formed in the phantoms by 5-second exposures with 5-second delays. Center to center spacing of individual lesions was 5.5 mm in either a linear pattern or a spiral pattern. Prior to the HIFU, 10 cycle tone bursts with 0.25% duty cycle were used to vaporize the droplets, forming an "acoustic trench" within 30 seconds. The transducer was then focused in the middle of the back bubble wall to form thermal lesions in the trench. All lesions were imaged optically and with 2T MRI. With the use of ADV and the acoustic trench, a uniform thermal ablation volume of 15 cm(3) was achieved in 4 minutes; without ADV only less than 15% of this volume was filled. The commonly seen tadpole shape characteristic of bubble-enhanced HIFU lesions was not evident with the acoustic trench. In conclusion, ADV shows promise for the spatial control and dramatic acceleration of thermal lesion production by HIFU.

Detection of cavernous transformation of the portal vein by contrast-enhanced ultrasound.

PubMed

Hwang, Misun; Thimm, Matthew A; Guerrerio, Anthony L

2018-06-01

Cavernous transformation of the portal vein can be missed on color Doppler exam or arterial phase cross-sectional imaging due to their slow flow and delayed enhancement. Contrast-enhanced ultrasound (CEUS) offers many advantages over other imaging techniques and can be used to successfully detect cavernous transformations of the portal vein. A 10-month-old female was followed for repeat episodes of hematemesis. Computed tomography angiography (CTA) and magnetic resonance arteriogram (MRA) and portal venography were performed. Color Doppler exam of the portal vein was performed followed by administration of Lumason, a microbubble US contrast agent. Magnetic resonance arteriogram, CTA, and color Doppler exam at the time of initial presentation was unremarkable without obvious vascular malformation within the limits of motion degraded exam. At 8-month follow-up, esophagogastroduodenoscopy revealed a vascular malformation in the distal esophagus which was sclerosed. At 6 month after sclerosis of the lesion, portal venography revealed occlusion of the portal vein with extensive collateralization. Color Doppler revealed subtle hyperarterialization and periportal collaterals. CEUS following color Doppler exam demonstrated extensive enhancement of periportal collaterals. Repeat color Doppler after contrast administration demonstrated extensive Doppler signal in the collateral vessels, suggestive of cavernous transformation. We describe a case of cavernous transformation of the portal vein missed on initial color Doppler, CTA and MRA, but detected with contrast-enhanced ultrasound technique.

Ultrasound in Space Medicine

NASA Technical Reports Server (NTRS)

Dulchavsky, Scott A.; Sargsyan, A.E.

2009-01-01

This slide presentation reviews the use of ultrasound as a diagnostic tool in microgravity environments. The goals of research in ultrasound usage in space environments are: (1) Determine accuracy of ultrasound in novel clinical conditions. (2) Determine optimal training methodologies, (3) Determine microgravity associated changes and (4) Develop intuitive ultrasound catalog to enhance autonomous medical care. Also uses of Ultrasound technology in terrestrial applications are reviewed.

Cumulative phase delay imaging for contrast-enhanced ultrasound tomography

NASA Astrophysics Data System (ADS)

Demi, Libertario; van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo

2015-11-01

Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization.

Cumulative phase delay imaging for contrast-enhanced ultrasound tomography.

PubMed

Demi, Libertario; van Sloun, Ruud J G; Wijkstra, Hessel; Mischi, Massimo

2015-11-07

Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization.

Research on respiratory motion correction method based on liver contrast-enhanced ultrasound images of single mode

NASA Astrophysics Data System (ADS)

Zhang, Ji; Li, Tao; Zheng, Shiqiang; Li, Yiyong

2015-03-01

To reduce the effects of respiratory motion in the quantitative analysis based on liver contrast-enhanced ultrasound (CEUS) image sequencesof single mode. The image gating method and the iterative registration method using model image were adopted to register liver contrast-enhanced ultrasound image sequences of single mode. The feasibility of the proposed respiratory motion correction method was explored preliminarily using 10 hepatocellular carcinomas CEUS cases. The positions of the lesions in the time series of 2D ultrasound images after correction were visually evaluated. Before and after correction, the quality of the weighted sum of transit time (WSTT) parametric images were also compared, in terms of the accuracy and spatial resolution. For the corrected and uncorrected sequences, their mean deviation values (mDVs) of time-intensity curve (TIC) fitting derived from CEUS sequences were measured. After the correction, the positions of the lesions in the time series of 2D ultrasound images were almost invariant. In contrast, the lesions in the uncorrected images all shifted noticeably. The quality of the WSTT parametric maps derived from liver CEUS image sequences were improved more greatly. Moreover, the mDVs of TIC fitting derived from CEUS sequences after the correction decreased by an average of 48.48+/-42.15. The proposed correction method could improve the accuracy of quantitative analysis based on liver CEUS image sequences of single mode, which would help in enhancing the differential diagnosis efficiency of liver tumors.

Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model

PubMed Central

Sutton, Jonathan T.; Ivancevich, Nikolas M.; Perrin, Stephen R.; Vela, Deborah C.; Holland, Christy K.

2013-01-01

Using an FDA-approved contrast agent (Definity®) and thrombolytic drug (rt-PA), we investigated ultrasound-enhanced thrombolysis in two whole-blood clot models. Porcine venous blood was collected from donor hogs and coagulated in two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombolysis model, while an intermittent ultrasound scheme previously developed to maximize stable cavitation was applied and acoustic emissions were detected. Exposure of clots to 3.15 μg/mL rt-PA promoted lysis in both clot models, compared to exposure to plasma alone. However, in the presence of rt-PA, Definity®, and ultrasound, only unretracted clots experienced significant enhancement of thrombolysis compared to treatment with rt-PA. In these clots, microscopy studies revealed loose erythrocyte aggregates, a significantly less extensive fibrin network, and a higher porosity, which may facilitate increase penetration of thrombolytics by cavitation. PMID:23453629

Effect of controlled offset of focal position in cavitation-enhanced high-intensity focused ultrasound treatment

NASA Astrophysics Data System (ADS)

Goto, Kota; Takagi, Ryo; Miyashita, Takuya; Jimbo, Hayato; Yoshizawa, Shin; Umemura, Shin-ichiro

2015-07-01

High-intensity focused ultrasound (HIFU) is a noninvasive treatment for tumors such as cancer. In this method, ultrasound is generated outside the body and focused to the target tissue. Therefore, physical and mental stresses on the patient are minimal. A drawback of the HIFU treatment is a long treatment time for a large tumor due to the small therapeutic volume by a single exposure. Enhancing the heating effect of ultrasound by cavitation bubbles may solve this problem. However, this is rather difficult because cavitation clouds tend to be formed backward from the focal point while ultrasonic intensity for heating is centered at the focal point. In this study, the focal points of the trigger pulses to generate cavitation were offset forward from those of the heating ultrasound to match the cavitation clouds with the heating patterns. Results suggest that the controlled offset of focal points makes the thermal coagulation more predictable.

[Value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant renal neoplasms].

PubMed

Zhang, Sheng; Wang, Xiao-qing; Xin, Xiao-jie; Xu, Yong

2013-05-01

To investigate the value of contrast enhanced ultrasound (CEUS) imaging in the differential diagnosis between benign and malignant renal neoplasms. Two hundred and forty-five cases of renal space-occupying lesions confirmed by biopsy or surgical pathology were included in this study. The CEUS features of the renal space-occupying lesions, i.e., the enhancement degree, homogeneity of enhancement, washing-in and washing-out time and enhancement pattern, were retrospectively analyzed. There were 210 cases of malignant renal tumors and 35 cases of benign lesions. The CEUS modes of the malignant renal tumors included "quick in and quick out" 82 cases, "quick in and slow out" 64 cases, "slow in and quick out" 18 cases and "slow in and slow out" 46 cases; good enhancement 150 cases (71.4%) and inhomogeneous enhancement 180 cases (85.7%).Both the contrast agent filling defect area and solid component enhancement of solid-cystic tumors were important features of malignant renal tumors. In the 35 cases of benign lesions,the CEUS modes included "quick in and quick out" 4 cases, "quick in and slow out" 8 cases, "slow in and quick out" 10 cases and "slow in and slow out" 13 cases. Most of the benign tumors showed low enhancement 51.4% (18/35) and inhomogeneous enhancement 54.3% (19/35). There were significant differences between the malignant and benign renal neoplasms in CEUS mode, degree of enhancement and homogeneity of enhancement (P < 0.05), and in time of increasing, peak time, peak intensity and peak intensity ratio (P < 0.05). The accuracy rates of contrast-enhanced ultrasound for diagnosis of benign and malignant tumors were 77.1% and 83.8%, respectively, while the two-dimensional ultrasound diagnosis of benign and malignant tumors were 68.6% and 76.7%, respectively, with a significant difference (P < 0.05). CEUS may provide more information to improve the diagnostic accuracy for renal neoplasms, and may play important role in differential diagnosis between benign and

Intense acoustic bursts as a signal-enhancement mechanism in ultrasound-modulated optical tomography.

PubMed

Kim, Chulhong; Zemp, Roger J; Wang, Lihong V

2006-08-15

Biophotonic imaging with ultrasound-modulated optical tomography (UOT) promises ultrasonically resolved imaging in biological tissues. A key challenge in this imaging technique is a low signal-to-noise ratio (SNR). We show significant UOT signal enhancement by using intense time-gated acoustic bursts. A CCD camera captured the speckle pattern from a laser-illuminated tissue phantom. Differences in speckle contrast were observed when ultrasonic bursts were applied, compared with when no ultrasound was applied. When CCD triggering was synchronized with burst initiation, acoustic-radiation-force-induced displacements were detected. To avoid mechanical contrast in UOT images, the CCD camera acquisition was delayed several milliseconds until transient effects of acoustic radiation force attenuated to a satisfactory level. The SNR of our system was sufficiently high to provide an image pixel per acoustic burst without signal averaging. Because of the substantially improved SNR, the use of intense acoustic bursts is a promising signal enhancement strategy for UOT.

Transabdominal contrast-enhanced ultrasound imaging of the prostate.

PubMed

Mischi, Massimo; Demi, Libertario; Smeenge, Martijn; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel

2015-04-01

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

CT and Ultrasound Guided Stereotactic High Intensity Focused Ultrasound (HIFU)

NASA Astrophysics Data System (ADS)

Wood, Bradford J.; Yanof, J.; Frenkel, V.; Viswanathan, A.; Dromi, S.; Oh, K.; Kruecker, J.; Bauer, C.; Seip, R.; Kam, A.; Li, K. C. P.

2006-05-01

To demonstrate the feasibility of CT and B-mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non-thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position-sensing arm and an active six degree-of-freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2-4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre-clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre-clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non-enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre-clinical models may be translated to large

Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model.

PubMed

Sutton, Jonathan T; Ivancevich, Nikolas M; Perrin, Stephen R; Vela, Deborah C; Holland, Christy K

2013-05-01

We investigated ultrasound-enhanced thrombolysis in two whole-blood clot models using a Food and Drug Administration-approved contrast agent (Definity, Lantheus Medical Imaging; Billerica, MA USA) and thrombolytic drug (recombinant tissue-type plasminogen activator [rt-PA]) (Genentech; South San Francisco, CA USA). Porcine venous blood was collected from donor hogs and coagulated in vials made of two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombosis model, and exposed to an intermittent ultrasound scheme previously developed to maximize stable cavitation while acoustic emissions were detected. Exposure to 3.15 μg/mL rt-PA promoted lysis in both clot models, compared with exposure to plasma alone. However, only unretracted clots experienced significant enhancement of thrombolysis in the presence of rt-PA, Definity, and ultrasound, compared with treatment with rt-PA. In these clots, microscopy revealed loose erythrocyte aggregates, a significantly less extensive fibrin network and a higher porosity, which may facilitate increased penetration of thrombolytics by cavitation. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound

PubMed Central

Wang, Z; Xu, H-X; Xie, X-Y; Xie, X-H; Kuang, M; Xu, Z-F; Liu, G-J; Chen, L-D; Lin, M-X; Lu, M-D

2010-01-01

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone. PMID:19723766

Using low frequency and intensity ultrasound to enhance start-up and operation performance of Anammox process inoculated with the conventional sludge.

PubMed

Wang, Tao; Zhang, Diandian; Sun, Yating; Zhou, Shanshan; Li, Lin; Shao, Jingjing

2018-04-01

A lab-scale ultrasound enhancing Anammox reactor (R1) was established and irradiated once a week by ultrasound with the optimal parameter (frequency of 25 kHz, intensity of 0.2 W cm -2 and exposure time of 3 min) obtained by batch experiments. R1 and the controlled Anammox reactor (R2) without exposure to the ultrasound were operated in parallel. The start-up period of Anammox process (53 days) in R1 was shorter than that (61 days) in R2. The nitrogen loading-enhancing period (day 53-day 135) in R1 was also shorter than that (day 61-day 151) in R2. At the end of the nitrogen loading-enhancing period, NLR (0.76 kg N m -3  d -1 ) and NRR (0.68 kg N m -3  d -1 ) of R1 were both higher than NLR (0.66 kg N m -3  d -1 ) and NRR (0.56 kg N m -3  d -1 ) of R2. Moreover, The stability of Anammox process in R1 was better than that in R2. The results demonstrated that the periodical irradiation of ultrasound enhanced the start-up and operational performance of Anammox reactor. Microbial community analysis indicated that the ultrasound accelerated the microbial succession from some other bacteria to Anammox bacteria so that shorten the start-up period of Anammox process from the conventional activated sludge. It also indicated that the ultrasound strengthened the competitive advantage of Candidatus Kuenenia stuttgartiensis in Anammox bacteria of the mature sludge so as to enhance the nitrogen removal performance of the Anammox reactor under the operation condition of high nitrogen loading. Copyright © 2017 Elsevier B.V. All rights reserved.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015

Medical Ultrasound Technology Research and Development at the University of Washington Center for Industrial and Medical Ultrasound

DTIC Science & Technology

2003-10-02

provide a world-class, advanced research center for bioengineering development and graduate education in high-intensity, focused ultrasound ( HIFU ). This...convenient, and robust. These technological enhancements have enabled the development of HIFU arrays and image-guided ultrasound systems for greater... Ultrasound (CIMU). The many disparate facilities and technical capabilities available to CIMU staff and students were integrated and enhanced to

Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

PubMed

He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

2017-12-01

This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

Driving delivery vehicles with ultrasound ☆

PubMed Central

Ferrara, Katherine W.

2009-01-01

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled “Ultrasound for Drug and Gene Delivery,” addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. PMID:18479775

Effect of ultrasound-enhanced fat separation on whey powder phospholipid composition and stability.

PubMed

Torkamani, Amir E; Juliano, Pablo; Fagan, Peter; Jiménez-Flores, Rafael; Ajlouni, Said; Singh, Tanoj K

2016-06-01

Fat from freshly pasteurized liquid whey was partially separated by gravity for 5, 10, and 30min, with and without simultaneous application of ultrasound. Ultrasound treatments were carried out at 400 and 1,000 kHz at different specific energy inputs (23-390 kJ/kg). The fat-enriched top layers (L1) and the fat-depleted bottom layers (L2) were separately removed and freeze-dried. Nonsonicated and sonicated L2 powders were stored for 14d at ambient temperature to assess their oxidative stability. Creaming was enhanced at both frequencies and fat separation increased with higher ultrasonic energy, extended sonication, or both. The oxidative volatile compound content decreased in defatted whey powders below published odor detection threshold values for all cases. Sonication had a minor influence on the partitioning of phospholipids with fat separation. The current study suggested that ultrasonication at high frequency enhanced fat separation from freshly pasteurized whey while improving whey powder oxidative stability. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

Fast microcalcification detection in ultrasound images using image enhancement and threshold adjacency statistics

NASA Astrophysics Data System (ADS)

Cho, Baek Hwan; Chang, Chuho; Lee, Jong-Ha; Ko, Eun Young; Seong, Yeong Kyeong; Woo, Kyoung-Gu

2013-02-01

The existence of microcalcifications (MCs) is an important marker of malignancy in breast cancer. In spite of the benefits in mass detection for dense breasts, ultrasonography is believed that it might not reliably detect MCs. For computer aided diagnosis systems, however, accurate detection of MCs has the possibility of improving the performance in both Breast Imaging-Reporting and Data System (BI-RADS) lexicon description for calcifications and malignancy classification. We propose a new efficient and effective method for MC detection using image enhancement and threshold adjacency statistics (TAS). The main idea of TAS is to threshold an image and to count the number of white pixels with a given number of adjacent white pixels. Our contribution is to adopt TAS features and apply image enhancement to facilitate MC detection in ultrasound images. We employed fuzzy logic, tophat filter, and texture filter to enhance images for MCs. Using a total of 591 images, the classification accuracy of the proposed method in MC detection showed 82.75%, which is comparable to that of Haralick texture features (81.38%). When combined, the performance was as high as 85.11%. In addition, our method also showed the ability in mass classification when combined with existing features. In conclusion, the proposed method exploiting image enhancement and TAS features has the potential to deal with MC detection in ultrasound images efficiently and extend to the real-time localization and visualization of MCs.

Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging

PubMed Central

Pysz, Marybeth A.; Guracar, Ismayil; Foygel, Kira; Tian, Lu; Willmann, Jürgen K.

2015-01-01

Purpose To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. Materials and methods The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis. Results MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05). Conclusion Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts. PMID:22535383

Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

PubMed

Pysz, Marybeth A; Guracar, Ismayil; Foygel, Kira; Tian, Lu; Willmann, Jürgen K

2012-09-01

To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis. MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05). Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts.

Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

PubMed

Li, Guo; Yan, Qiang; Xia, Hesheng; Zhao, Yue

2015-06-10

Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.

Analysis of achilles tendon vascularity with second-generation contrast-enhanced ultrasound.

PubMed

Genovese, Eugenio; Ronga, Mario; Recaldini, Chiara; Fontana, Federico; Callegari, Leonardo; Maffulli, Nicola; Fugazzola, Carlo

2011-01-01

To compare morphological, power Doppler, and contrast-enhanced ultrasound (CEUS) features of the Achilles tendon between asymptomatic athletes and athletes who had undergone surgical repair of a previous rupture. Twenty-four athletes were divided in two groups (A and B). Group A included 14 patients with a median age of 32 years (range 27 to 47 years) who had undergone surgical repair for unilateral Achilles tendon rupture. Group B (control group) included 10 subjects with a median age of 34 years (range 27 to 40 years) with no previous or present history of tendinopathy. All patients were evaluated with ultrasound, power Doppler, and CEUS with second-generation contrast agent. We studied the uninjured Achilles tendon in athletes of group A and either the left or the right Achilles tendon of the athletes in group B. CEUS showed a significantly greater ability to detect a greater number of vascular spots within the uninjured tendon of group A compared to group B (<0.05). In athletes who had suffered a tear of an Achilles tendon, CEUS detected small vessels that were not identified by power Doppler ultrasound in the uninjured contralateral Achilles tendon. CEUS is useful to evaluate vascularity not detected by other imaging techniques. Vascularity in the uninjured tendon seems to be increased in patients who had a previous rupture. Copyright © 2011 Wiley Periodicals, Inc.

Partial segmental thrombosis of the corpus cavernosum (PSTCC) diagnosed by contrast-enhanced ultrasound: a case report.

PubMed

Sauer, Stephanie; Goltz, Jan P; Gassenmaier, Tobias; Kunz, Andreas S; Bley, Thorsten A; Klein, Detlef; Petritsch, Bernhard

2014-12-17

Partial segmental thrombosis of the corpus cavernosum (PSTCC) is a rare disease predominantly occurring in young men. Cardinal symptoms are pain and perineal swelling. Although several risk factors are described in the literature, the exact etiology of penile thrombosis remains unclear in most cases. MRI or ultrasound (US) is usually used for diagnosing this condition. We report a case of penile thrombosis after left-sided varicocele ligature in a young patient. The diagnosis was established using contrast-enhanced ultrasound (CEUS) and was confirmed by contrast-enhanced magnetic resonance imaging (ceMRI). Successful conservative treatment consisted of systemic anticoagulation using low molecular weight heparin and acetylsalicylic acid. PSTCC is a rare condition in young men and appears with massive pain and perineal swelling. In case of suspected PSTCC utilization of CEUS may be of diagnostic benefit.

Pulsed high intensity focused ultrasound (pHIFU) enhances delivery of doxorubicin in a preclinical model of pancreatic cancer

PubMed Central

Li, Tong; Wang, Yak-Nam; Khokhlova, Tatiana D.; D’Andrea, Samantha; Starr, Frank; Chen, Hong; McCune, Jeannine S.; Risler, Linda J.; Mashadi-Hossein, Afshin; Hwang, Joo Ha

2015-01-01

Pancreatic cancer is characterized by extensive stromal desmoplasia which decreases blood perfusion and impedes chemotherapy delivery. Breaking the stromal barrier could both increase perfusion and permeabilize the tumor, enhancing chemotherapy penetration. Mechanical disruption of the stroma can be achieved using ultrasound-induced bubble activity – cavitation. Cavitation is also known to result in microstreaming and could have the added benefit of actively enhancing diffusion into the tumors. Here, we report the ability to enhance chemotherapeutic drug doxorubicin (Dox) penetration using ultrasound-induced cavitation in a genetically engineered mouse model (KPC mouse) of pancreatic ductal adenocarcinoma. To induce localized inertial cavitation in pancreatic tumors, pulsed high intensity focused ultrasound (pHIFU) was used either during or before doxorubicin administration to elucidate the mechanisms of enhanced drug delivery (active versus passive drug diffusion). For both types, the pHIFU exposures which were associated with high cavitation activity resulted in disruption of the highly fibrotic stromal matrix and enhanced the normalized Dox concentration by up to 4.5 fold compared to controls. Furthermore, normalized Dox concentration was associated with the cavitation metrics (p < 0.01), indicating that high and sustained cavitation results in increased chemotherapy penetration. No significant difference between the outcomes of the two types, i.e., Dox infusion during or after pHIFU treatment, was observed, suggesting that passive diffusion into previously permeabilized tissue is the major mechanism for the increase in drug concentration. Together, the data indicate that pHIFU treatment of pancreatic tumors when resulting in high and sustained cavitation can efficiently enhance chemotherapy delivery to pancreatic tumors. PMID:26216548

Combination of bubble liposomes and high-intensity focused ultrasound (HIFU) enhanced antitumor effect by tumor ablation.

PubMed

Hamano, Nobuhito; Negishi, Yoichi; Takatori, Kyohei; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo; Niidome, Takuro; Aramaki, Yukihiko

2014-01-01

Ultrasound (US) is used in the clinical setting not only for diagnosis but also for therapy. As a therapeutic US technique, high-intensity focused ultrasound (HIFU) can be applied to treat cancer in a clinical setting. Microbubbles increased temperature and improved the low therapeutic efficiency under HIFU; however, microbubbles have room for improvement in size, stability, and targeting ability. To solve these issues, we reported that "Bubble liposomes" (BLs) containing the US imaging gas (perfluoropropane gas) liposomes were suitable for ultrasound imaging and gene delivery. In this study, we examined whether BLs and HIFU could enhance the ablation area of the tumor and the antitumor effect. First, we histologically analyzed the tumor after BLs and HIFU. The ablation area of the treatment of BLs and HIFU was broader than that of HIFU alone. Next, we monitored the temperature of the tumor, and examined the antitumor effect. The temperature increase with BLs and HIFU treatment was faster and higher than that with HIFU alone. Moreover, treatment with BLs and HIFU enhanced the antitumor effect, which was better than with HIFU alone. Thus, the combination of BLs and HIFU could be efficacious for cancer therapy.

Contrast enhanced ultrasound of renal masses. A reappraisal of EFSUMB recommendations and possible emerging applications.

PubMed

Sparchez, Zeno; Radu, Pompilia; Sparchez, Mihaela; Crisan, Nicolae; Kacso, Gabriel; Petrut, Bogdan

2015-06-01

The main imagistic method for characterization of renal lesions is contrast enhanced computed tomography (CECT). Disadvantages of CECT are a contrast-induced nephropathy in patients with renal impairment, allergic reactions and high costs. Contrast-enhanced ultrasound (CEUS) evaluation of hepatic and non-hepatic lesions is a relatively new, but increasingly utilised, diagnostic method. In 2011 the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) updated the Guidelines and Recommendations on the Clinical Practice of CEUS and included in the recommendation the renal pathology. However, there are several possible new indications that have not been discussed (pyelocaliceal masses and renal vein thrombosis) and several issues that remain controversial such as the differentiation of benign and malignant tumours or the differentiation of lymphoma and metastasis. This study aims to review literature data, as well as reveal the latest findings in the field of renal CEUS.

Improved Contrast-Enhanced Ultrasound Imaging With Multiplane-Wave Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2018-02-01

Contrast-enhanced ultrasound (CEUS) imaging has great potential for use in new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, contrast agents (i.e., microbubbles) are used to improve contrast between blood and tissue because of their high nonlinearity under low ultrasound pressure. However, the quality of CEUS imaging sometimes suffers from a low signal-to-noise ratio (SNR) in deeper imaging regions when a low mechanical index (MI) is used to avoid microbubble disruption, especially for imaging at off-resonance transmit frequencies. In this paper, we propose a new strategy of combining CEUS sequences with the recently proposed multiplane-wave (MW) compounding method to improve the SNR of CEUS in deeper imaging regions without increasing MI or sacrificing frame rate. The MW-CEUS method emits multiple Hadamard-coded CEUS pulses in each transmission event (i.e., pulse-echo event). The received echo signals first undergo fundamental bandpass filtering (i.e., the filter is centered on the transmit frequency) to eliminate the microbubble's second-harmonic signals because they cannot be encoded by pulse inversion. The filtered signals are then Hadamard decoded and realigned in fast time to recover the signals as they would have been obtained using classic CEUS pulses, followed by designed recombination to cancel the linear tissue responses. The MW-CEUS method significantly improved contrast-to-tissue ratio and SNR of CEUS imaging by transmitting longer coded pulses. The image resolution was also preserved. The microbubble disruption ratio and motion artifacts in MW-CEUS were similar to those of classic CEUS imaging. In addition, the MW-CEUS sequence can be adapted to other transmission coding formats. These properties of MW-CEUS can potentially facilitate CEUS imaging for many clinical applications, especially assessing deep abdominal organs or the heart.

Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

PubMed

Bhatnagar, Sunali; Kwan, James J; Shah, Apurva R; Coussios, Constantin-C; Carlisle, Robert C

2016-09-28

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'. In vivo murine studies indicated that nanocup-assisted ultrasound transdermal vaccination achieved significantly (p<0.05) higher delivery doses without visible skin damage compared to the use of a chemical penetration enhancer. Transdermal OVA doses of up to 1μg were achieved in a single 90-second treatment, which was sufficient to trigger an antigen-specific immune response. Furthermore, ultrasound-assisted vaccine delivery in the presence of nanocups demonstrated substantially higher specific anti-OVA IgG antibody levels compared to other transdermal methods. Further optimisation can lead to a viable, safe and non-invasive delivery platform for vaccines with potential use in a primary care setting or personalized self-vaccination at home. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Contrast-enhanced ultrasound in diagnosis and characterization of focal hepatic lesions.

PubMed

Molins, Inés Gómez; Font, Juan Manuel Fernández; Alvaro, Juan Carrero; Navarro, Jose Luís Lledó; Gil, Marta Fernández; Rodríguez, Conrado M Fernández

2010-12-28

The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases, has led to an important increase in identification of focal liver lesions. The development of contrast-enhanced ultrasound (CEUS) opens a new window in the diagnosis and follow-up of these lesions. This technique offers obvious advantages over the computed tomography and magnetic resonance, without a decrease in its sensitivity and specificity. The new second generation contrast agents, due to their intravascular distribution, allow a continuous evaluation of the enhancement pattern, which is crucial in characterization of liver lesions. The dual blood supply in the liver shows three different phases, namely arterial, portal and late phases. The enhancement during portal and late phases can give important information about the lesion's behavior. Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis. The role of emerging techniques as a contrast-enhanced three-dimensional US is also discussed. In this article, the advantages, indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed.

Contrast-enhanced ultrasound in diagnosis and characterization of focal hepatic lesions

PubMed Central

Molins, Inés Gómez; Font, Juan Manuel Fernández; Álvaro, Juan Carrero; Navarro, Jose Luís Lledó; Gil, Marta Fernández; Rodríguez, Conrado M Fernández

2010-01-01

The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases, has led to an important increase in identification of focal liver lesions. The development of contrast-enhanced ultrasound (CEUS) opens a new window in the diagnosis and follow-up of these lesions. This technique offers obvious advantages over the computed tomography and magnetic resonance, without a decrease in its sensitivity and specificity. The new second generation contrast agents, due to their intravascular distribution, allow a continuous evaluation of the enhancement pattern, which is crucial in characterization of liver lesions. The dual blood supply in the liver shows three different phases, namely arterial, portal and late phases. The enhancement during portal and late phases can give important information about the lesion’s behavior. Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis. The role of emerging techniques as a contrast-enhanced three-dimensional US is also discussed. In this article, the advantages, indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed. PMID:21225000

Contrast-enhanced ultrasound features of hepatocellular carcinoma not detected during the screening procedure.

PubMed

Dong, Yi; Wang, Wen-Ping; Mao, Feng; Dietrich, Christoph

2017-08-01

Aim  The aim of this retrospective study is to report on the characteristics of contrast-enhanced ultrasound (CEUS) of primarily not detected hepatocellular carcinoma (HCC) during the screening procedure of patients at risk. Methods  Sixty-four patients with a finally solitary and histologically proven HCC not detected HCC during the screening procedure were retrospectively analyzed. Most of HCC lesions (90.6 %, 58/64) measured < 20 mm in diameter. All HCC lesions were not detected during the initial screening procedure but suspected using contrast-enhanced magnetic resonance imaging. The final gold standard was biopsy or surgery with histological examination. Results  On CEUS, 62/64 (96.8 %) of HCC were characterized as an obviously hyperenhanced lesion in arterial phase, and 41/64 (64.1 %) of HCC were characterized as hypoenhancing lesions in the portal venous and late phases. During the arterial phase of CEUS, 96.8 % of HCC displayed homogeneous hyperenhancement. Knowing the CEUS and magnetic resonance imaging findings, 45/64 (70.3 %) could have been detected using B-mode ultrasound (BMUS). Conclusion  BMUS as a screening procedure is generally accepted. Contrast-enhanced imaging modalities have improved detection and characterization of HCC. Homogeneous hyperenhancement during the arterial phase and mild washout are indicative for HCC in liver cirrhosis. © Georg Thieme Verlag KG Stuttgart · New York.

Phase-shift perfluorocarbon agents enhance high intensity focused ultrasound thermal delivery with reduced near-field heating

PubMed Central

Phillips, Linsey C.; Puett, Connor; Sheeran, Paul S.; Dayton, Paul A.; Wilson Miller, G.; Matsunaga, Terry O.

2013-01-01

Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100–300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 × 106 per cm3 resulted in mean lesion volumes of 80.4 ± 33.1 mm3 and 52.8 ± 14.2 mm3 (mean ± s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, compared to a lesion volume of 1.0 ± 0.8 mm3 in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site. PMID:23927187

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Short Version).

PubMed

Sidhu, Paul S; Cantisani, Vito; Dietrich, Christoph F; Gilja, Odd Helge; Saftoiu, Adrian; Bartels, Eva; Bertolotto, Michele; Calliada, Fabrizio; Clevert, Dirk-André; Cosgrove, David; Deganello, Annamaria; D'Onofrio, Mirko; Drudi, Francesco Maria; Freeman, Simon; Harvey, Christopher; Jenssen, Christian; Jung, Ernst-Michael; Klauser, Andrea Sabine; Lassau, Nathalie; Meloni, Maria Franca; Leen, Edward; Nicolau, Carlos; Nolsoe, Christian; Piscaglia, Fabio; Prada, Francesco; Prosch, Helmut; Radzina, Maija; Savelli, Luca; Weskott, Hans-Peter; Wijkstra, Hessel

2018-04-01

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications. © Georg Thieme Verlag KG Stuttgart · New York.

Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

NASA Astrophysics Data System (ADS)

Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

2016-06-01

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina.

PubMed

Thakur, Sachin S; Ward, Micheal S; Popat, Amirali; Flemming, Nicole B; Parat, Marie-Odile; Barnett, Nigel L; Parekh, Harendra S

2017-01-01

Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye.

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

PubMed Central

Thakur, Sachin S.; Ward, Micheal S.; Popat, Amirali; Flemming, Nicole B.; Parat, Marie-Odile; Barnett, Nigel L.

2017-01-01

Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye. PMID:28542473

Microbubble and ultrasound radioenhancement of bladder cancer

PubMed Central

Tran, W T; Iradji, S; Sofroni, E; Giles, A; Eddy, D; Czarnota, G J

2012-01-01

Background: Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation. Methods: Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals). Results: Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation. Conclusion: Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death. PMID:22790798

A New Feature-Enhanced Speckle Reduction Method Based on Multiscale Analysis for Ultrasound B-Mode Imaging.

PubMed

Kang, Jinbum; Lee, Jae Young; Yoo, Yangmo

2016-06-01

Effective speckle reduction in ultrasound B-mode imaging is important for enhancing the image quality and improving the accuracy in image analysis and interpretation. In this paper, a new feature-enhanced speckle reduction (FESR) method based on multiscale analysis and feature enhancement filtering is proposed for ultrasound B-mode imaging. In FESR, clinical features (e.g., boundaries and borders of lesions) are selectively emphasized by edge, coherence, and contrast enhancement filtering from fine to coarse scales while simultaneously suppressing speckle development via robust diffusion filtering. In the simulation study, the proposed FESR method showed statistically significant improvements in edge preservation, mean structure similarity, speckle signal-to-noise ratio, and contrast-to-noise ratio (CNR) compared with other speckle reduction methods, e.g., oriented speckle reducing anisotropic diffusion (OSRAD), nonlinear multiscale wavelet diffusion (NMWD), the Laplacian pyramid-based nonlinear diffusion and shock filter (LPNDSF), and the Bayesian nonlocal means filter (OBNLM). Similarly, the FESR method outperformed the OSRAD, NMWD, LPNDSF, and OBNLM methods in terms of CNR, i.e., 10.70 ± 0.06 versus 9.00 ± 0.06, 9.78 ± 0.06, 8.67 ± 0.04, and 9.22 ± 0.06 in the phantom study, respectively. Reconstructed B-mode images that were developed using the five speckle reduction methods were reviewed by three radiologists for evaluation based on each radiologist's diagnostic preferences. All three radiologists showed a significant preference for the abdominal liver images obtained using the FESR methods in terms of conspicuity, margin sharpness, artificiality, and contrast, p<0.0001. For the kidney and thyroid images, the FESR method showed similar improvement over other methods. However, the FESR method did not show statistically significant improvement compared with the OBNLM method in margin sharpness for the kidney and thyroid images. These results demonstrate

Enhanced Thermal Ablation by Combining Ultrasound Contrast Agents with a Miniature Flat Transducer

NASA Astrophysics Data System (ADS)

Murillo, A.; Goldendstedt, C.; Lafon, C.; Cathignol, D.; Chapelon, J.-Y.

2007-05-01

Miniature transducers can be used for performing interstitial thermal ablation. Increasing the frequency of non-focused transducers enhances energy deposition but limits the therapeutic range. In order to treat extended tumors, new therapeutic strategies must be explored. This work aimed to combine ultrasound contrast agents (UCA) with flat transducers for increasing the treatment depth. The idea consists in increasing attenuation away from the transducer to favor remote heat deposition. Thermal ablation is induced in three steps. 1- Attenuation raises by injecting UCA; 2- Destruction of bubbles next to the transducer by pulsed high intensity bursts, results in a gradient of attenuation; 3- Continuous ultrasound are applied for generating a localized thermal lesion. In vitro tests were performed on temperature-sensitive tissue phantoms in which the UCA BR14 (Bracco) was injected during the liquid phase. The feasibility of the idea was demonstrated in three stages. 1- The coefficient of attenuation was measured with the force balance as a function of the concentration of BR14. For 0.8 and 4.8% attenuation at 10MHz was found to be 0.35 and 1.33 Np/cm respectively. 2- Pulsed ultrasound was applied on phantoms to destroy UCA. Based on the echogenicity decay evidenced on ultrasound images, a 1MPa-pressure was required at 10MHz. 3- Heating beams were applied on phantoms presenting a gradient in attenuation. Lesions were 1.5 times larger than in phantoms with constant attenuation. This study demonstrates that UCA can be selectively destroyed in order to generate a gradient of attenuation and extended thermal lesions.

Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

PubMed Central

Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

2016-01-01

The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P < 0.05). Subgroups MEUS1 (0.346 ± 0.345 g) and MEUS2 (2.232 ± 2.256 g) exhibited significantly lower post-treatment bleeding weight than the US and MB groups (5.698 ± 1.938 and 5.688 ± 2.317 g, respectively; all, P < 0.05). Additionally, MEUS subgroups 1–3 exhibited significantly lower post-treatment blood perfusion levels (PI ratios, 0.64 ± 0.085, 0.73 ± 0.045, and 0.84 ± 0.034, respectively) than the US and MB groups (PI ratios, 1.00 ± 0.005 and 0.99 ± 0.005, respectively; all, P < 0.05). In the MEUS group, hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound

PubMed Central

Kleinert, Stefan; Roll, Petra; Baumgaertner, Christian; Himsel, Andrea; Mueller, Adelheid; Fleck, Martin; Feuchtenberger, Martin; Jenett, Manfred; Tony, Hans-Peter

2012-01-01

Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID:22670165

Breast tumor size assessment: comparison of conventional ultrasound and contrast-enhanced ultrasound.

PubMed

Jiang, Yu-Xin; Liu, He; Liu, Ji-Bin; Zhu, Qing-Li; Sun, Qiang; Chang, Xiao-Yan

2007-12-01

Accurate assessment of tumor size is necessary when selecting patients for breast-conserving surgery. In the study of breast contrast-enhanced ultrasound (CEUS), we found that tumor size discrepancy between CEUS and conventional ultrasound (US) existed in some breast lesions, for which the reasons are not clear. Breast CEUS examinations were performed in 104 patients with breast lesions. The measurement of the 104 breast tumors on conventional US was obtained and compared with the measurement on CEUS. A difference in measuring tumor size of >3 mm for tumors up to 1.7 cm and 4 mm for tumors >or=1.7 cm, was defined as a significant discrepancy between conventional US and CEUS. The histopathological examination of size discrepancy was performed and the margin characteristics of breast cancers with larger measurements were compared with those with unchanged measurements. Among the 104 lesions (43 malignant, 60 benign, 1 borderline), the size of 27 breast cancers and one granulomatous mastitis appeared larger at CEUS. Pathologic examinations of the region corresponding to the measurement discrepancy were mainly ductal carcinomas in situ (DCIS), invasive carcinoma with a DCIS component, adenosis with lobular hyperplasia in breast cancers and inflammatory cell infiltration in one granulomatous mastitis. Well-defined margin characteristics were significantly different between breast cancers with larger measurements at CEUS and those with unchanged measurements of size (p = 0.002), whereas no significant difference was found between the two groups in ill-defined, spiculated, hyperechoic halo, microlobulated and angulated margins (p = 0.463, 0.117, 0.194, 0.666 and 0.780, respectively). This initial study suggests that significant discrepancy of breast lesion measurement between conventional US and CEUS is more likely presented in breast cancer than benign lesions. The pathologic findings corresponding to the region of size increased at CEUS are malignant in most malignant

Enhancing mung bean hydration using the ultrasound technology: description of mechanisms and impact on its germination and main components

NASA Astrophysics Data System (ADS)

Miano, Alberto Claudio; Pereira, Jessica Da Costa; Castanha, Nanci; Júnior, Manoel Divino Da Matta; Augusto, Pedro Esteves Duarte

2016-12-01

The ultrasound technology was successfully used to improve the mass transfer processes on food. However, the study of this technology on the grain hydration and on its main components properties was still not appropriately described. This work studied the application of the ultrasound technology on the hydration process of mung beans (Vigna radiata). This grain showed sigmoidal hydration behavior with a specific water entrance pathway. The ultrasound reduced ~25% of the hydration process time. In addition, this technology caused acceleration of the seed germination - and some hypothesis for this enhancement were proposed. Moreover, it was demonstrated that the ultrasound did not change both structure and pasting properties of the bean starch. Finally, the flour rheological properties proved that the ultrasound increased its apparent viscosity, and as the starch was not modified, this alteration was attributed to the proteins. All these results are very desirable for industry since the ultrasound technology improves the hydration process without altering the starch properties, accelerates the germination process (that is important for the malting and sprouting process) and increases the flour apparent viscosity, which is desirable to produce bean-based products that need higher consistency.

Investigation of the acute plantar fasciitis with contrast-enhanced ultrasound and shear wave elastography - first results.

PubMed

Putz, Franz Josef; Hautmann, Matthias G; Banas, Miriam C; Jung, Ernst Michael

2017-01-01

The plantar fasciitis is a common disease with a high prevalence in public and a frequent cause of heel pain. In our pilot study, we wanted to characterise the feasibility of shear-wave elastography and contrast-enhanced ultrasound (CEUS) in the assessment of the plantar fasciitis. 23 cases of painful heels were examined by B-Mode ultrasound, Power Doppler (PD), shear wave elastography and contrast-enhanced ultrasound before anti-inflammatory radiation. Time-intensity-curves were analysed by the integrated software. The results for area-under-the-curve (AUC), peak, time-to-peak (TTP) and mean-transit-time (MTT) were compared between the plantar fascia and the surrounding tissue. All cases showed thickening of the plantar fascia, in most cases with interstitial oedema (87.0%). Shear wave elastography showed inhomogeneous stiffness of the plantar fascia. 83.3% of cases showed a visible hyperperfusion in CEUS at the proximal plantar fascia in comparison to the surrounding tissue. This hyperperfusion could also be found in 75.0% of cases with no signs of vascularisation in PD. AUC (p = 0.0005) and peak (p = 0.037) were significantely higher in the plantar fascia than in the surrounding tissue. CEUS and shear wave elastography are new diagnostic tools in the assessment of plantar fasciitis and can provide quantitative parameters for monitoring therapy.

Applicability of contrast-enhanced ultrasound in the diagnosis of plantar fasciitis.

PubMed

Broholm, R; Pingel, J; Simonsen, L; Bülow, J; Johannsen, F

2017-12-01

Contrast-enhanced ultrasound (CEUS) is used to visualize the microvascularization in various tissues. The purpose of this study was to investigate whether CEUS could be used to visualize the microvascular volume (MV) in the plantar fascia, and to compare the method to clinical symptoms and B-mode ultrasound (US) in patients with plantar fasciitis (PF). Twenty patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5), and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat pad were measured independently by two observers. Inter- and intra-observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients, a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter-observer correlation as well as intra-observer agreement was excellent. The MV in the plantar fascia and plantar fat pad can be measured reliably using CEUS, suggesting that it is a reproducible method to examine patients with plantar fasciitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ultrasound pretreatment for enhanced biogas production from olive mill wastewater.

PubMed

Oz, Nilgun Ayman; Uzun, Alev Cagla

2015-01-01

This study investigates applicability of low frequency ultrasound technology to olive mill wastewaters (OMWs) as a pretreatment step prior to anaerobic batch reactors to improve biogas production and methane yield. OMWs originating from three phase processes are characterized with high organic content and complex nature. The treatment of the wastewater is problematic and alternative treatment options should be investigated. In the first part of the study, OMW samples were subjected to ultrasound at a frequency of 20kHz with applied powers varying between 50 and 100W under temperature controlled conditions for different time periods in order to determine the most effective sonication conditions. The level of organic matter solubilization at ultrasound experiments was assessed by calculating the ratio of soluble chemical oxygen demand/total chemical oxygen demand (SCOD/TCOD). The results revealed that the optimum ultrasonic condition for diluted OMW is 20kHz, 0.4W/mL for 10min. The application of ultrasound to OMW increased SCOD/TCOD ratio from 0.59 to 0.79. Statistical analysis (Friedman's tests) show that ultrasound was significantly effective on diluted OMW (p<0.05) in terms of SCOD parameter, but not for raw OMW (p>0.05). For raw OMW, this increase has been found to be limited due to high concentration of suspended solids (SS). In the second part of the study, biogas and methane production rates of anaerobic batch reactor fed with the ultrasound pretreated OMW samples were compared with the results of control reactor fed with untreated OMW in order to determine the effect of sonication. A nonparametric statistical procedure, Mann-Whitney U test, was used to compare biogas and methane production from anaerobic batch reactors for control and ultrasound pretreated samples. Results showed that application of low frequency ultrasound to OMW significantly improved both biogas and methane production in anaerobic batch reactor fed with the wastewater (p<0.05). Anaerobic

Assessment and classification of fistula-in-ano in patients with Crohn's disease by hydrogen peroxide enhanced transanal ultrasound.

PubMed

Sloots, C E; Felt-Bersma, R J; Poen, A C; Cuesta, M A; Meuwissen, S G

2001-09-01

Crohn's disease is well known for its perianal complications, among which fistulas-in-ano are the most common abnormalities. Fistulas-in-ano in Crohn's disease tend to be complex and have a high recurrence rate. Therefore the role of surgery is generally more conservative. Hydrogen peroxide enhanced transanal ultrasound has proven superior to physical examination, fistulography, computed tomography, and conventional ultrasound in demonstrating the fistula tract. This study examined the fistula tracks in patients with Crohn's disease. Forty-one patients with Crohn's disease and fistula-in-ano were investigated using physical examination, sondage of the fistula, proctoscopy and transanal ultrasound. Hydrogen peroxide was infused via a small catheter into the fistula. The main track and the ramification of the fistula were classified according to the anatomical Parks' classification. Only 9 (22%) patients had a single inter- or transsphincteric fistula. In 5 (12%) patients a single supra- or extrasphincteric fistula (high fistula) was found, in 14 (34%) more than one fistula track (ramified), and in 13 (32%) an anovaginal fistula. Thus 78% of patients had a surgically difficult to treat fistula. In the ramified fistula the main track follows the Parks' classification, but ramifications can have a bizarre pattern which is not in agreement with this classification. Optimal documentation by means of hydrogen peroxide enhanced transanal ultrasound is therefore mandatory before surgery or before other therapies such as anti-tumor necrosis factor treatment.

Ultrasound enhanced glucose release from corn in ethanol plants.

PubMed

Khanal, Samir Kumar; Montalbo, Melissa; van Leeuwen, J; Srinivasan, Gowrishankar; Grewell, David

2007-12-01

This work evaluated the use of high power ultrasonic energy to treat corn slurry in dry corn milling ethanol plants to enhance liquefaction and saccharification for ethanol production. Corn slurry samples obtained before and after jet cooking were subjected to ultrasonic pretreatment for 20 and 40 s at amplitudes of vibration ranging from 180 to 299 microm(pp) (peak to peak amplitude in microm). The resulting samples were then exposed to enzymes (alpha-amylase and glucoamylase) to convert cornstarch into glucose. A comparison of scanning electron micrographs of raw and sonicated samples showed the development of micropores and the disruption of cell walls in corn mash. The corn particle size declined nearly 20-fold following ultrasonic treatment at high power settings. The glucose release rate from sonicated samples increased as much as threefold compared to the control group. The efficiency of ultrasound exceeded 100% in terms of energy gain from the sugar released over the ultrasonic energy supplied. Enzymatic activity was enhanced when the corn slurry was sonicated with simultaneous addition of enzymes. This finding suggests that the ultrasonic energy did not degrade or denature the enzymes during the pretreatment.

Hilar biliary neurofibroma without neurofibromatosis: case report with contrast-enhanced ultrasound findings.

PubMed

Guo, Huan-Ling; Chen, Li-da; Wang, Zhu; Huang, Yang; Liu, Jin-Ya; Shan, Quan-Yuan; Xie, Xiao-Yan; Lu, Ming-de; Wang, Wei

2016-10-01

Solitary neurofibroma located in the hilum of the liver is extremely rare, particularly without neurofibromatosis. We herein report a case of hilar biliary neurofibroma without signs of von Recklinghausen's disease. A 36-year-old man was admitted to our department with progressive jaundice. The case was diagnosed as hilar cholangiocarcinoma based on preoperative imaging. The patient consequently received a Roux-en-Y hepaticojejunostomy and was confirmed with neurofibroma pathologically. This is the first reported imaging finding of hilar biliary neurofibroma using contrast-enhanced ultrasound, emphasizing the differential diagnosis of biliary tumors.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method.

PubMed

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-17

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat 'brighter' than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method

NASA Astrophysics Data System (ADS)

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-01

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat ‘brighter’ than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Ultrasound enhanced sanitizer efficacy in reduction of Escherichia coli O157:H7 population on spinach leaves

USDA-ARS?s Scientific Manuscript database

The use of ultrasound to enhance the efficacy of selected sanitizers in reduction of Escherichia coli O157:H7 populations on spinach was investigated. Spot-inoculated spinach samples were treated with water, chlorine, acidified sodium chlorite (ASC), peroxyacetic acid (POAA), and acidic electrolyzed...

Perfusion quantification in contrast-enhanced ultrasound (CEUS)--ready for research projects and routine clinical use.

PubMed

Tranquart, F; Mercier, L; Frinking, P; Gaud, E; Arditi, M

2012-07-01

With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers. © Georg Thieme Verlag KG Stuttgart · New York.

Time-reversal Techniques in Ultrasound-assisted Convection-enhanced Drug Delivery to the Brain: Technology Development and In Vivo Evaluation

PubMed Central

Lewis, George K.; Guarino, Sabrina; Gandhi, Gaurav; Filinger, Laurent; Lewis, George K.; Olbricht, Willam L.; Sarvazyan, Armen

2011-01-01

We describe a drug delivery method that combines Time-Reversal Acoustics (TRA) with Convection-Enhanced Delivery (CED) to improve the delivery of therapeutics to the interstitium of the brain. The Ultrasound-assisted CED approach (UCED) circumvents the blood-brain barrier by infusing compounds through a cannula that is inserted into the brain while simultaneously delivering ultrasound to improve the penetration of pharmaceuticals. CED without ultrasound-assistance has been used to treat a variety of neural disorders, including glioblastoma multiforme, a malignancy that presents a very poor prognosis for patients. We describe a novel system that is used to infuse fluids into the brain parenchyma while simultaneously exposing the tissue to safe levels of 1-MHz, low intensity, ultrasound energy. The system includes a combined infusion needle-hydrophone, a 10-channel ultralow-output impedance amplifier, a broad-band ultrasound resonator, and MatLab®-based TRA control and user-interface. TRA allows easy coupling of ultrasound therapy through the skull without complex phase-correction and array design. The smart targeting UCED system has been tested in vivo and results show it provides 1.5-mm spatial resolution for UCED and improves tracer distribution in the brain over CED alone. PMID:21881622

Adaptive windowing in contrast-enhanced intravascular ultrasound imaging

PubMed Central

Lindsey, Brooks D.; Martin, K. Heath; Jiang, Xiaoning; Dayton, Paul A.

2016-01-01

Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200 µm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2 dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2 dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium. PMID:27161022

Adaptive windowing in contrast-enhanced intravascular ultrasound imaging.

PubMed

Lindsey, Brooks D; Martin, K Heath; Jiang, Xiaoning; Dayton, Paul A

2016-08-01

Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200μm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasound pretreatment of filamentous algal biomass for enhanced biogas production.

PubMed

Lee, Kwanyong; Chantrasakdakul, Phrompol; Kim, Daegi; Kong, Mingeun; Park, Ki Young

2014-06-01

The filamentous alga Hydrodictyon reticulatum harvested from a bench-scale wastewater treatment pond was used to evaluate biogas production after ultrasound pretreatment. The effects of ultrasound pretreatment at a range of 10-5000 J/mL were tested with harvested H. reticulatum. Cell disruption by ultrasound was successful and showed a higher degree of disintegration at a higher applied energy. The range of 10-5000 J/mL ultrasound was able to disintegrated H. reticulatum and the soluble COD was increased from 250 mg/L to 1000 mg/L at 2500 J/mL. The disintegrated algal biomass was digested for biogas production in batch experiments. Both cumulative gas generation and volatile solids reduction data were obtained during the digestion. Cell disintegration due to ultrasound pretreatment increased the specific biogas production and degradation rates. Using the ultrasound approach, the specific methane production at a dose of 40 J/mL increased up to 384 mL/g-VS fed that was 2.3 times higher than the untreated sample. For disintegrated samples, the volatile solids reduction was greater with increased energy input, and the degradation increased slightly to 67% at a dose of 50 J/mL. The results also indicate that disintegration of the algal cells is the essential step for efficient anaerobic digestion of algal biomass. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biopsy of Liver Target Lesions under Contrast-Enhanced Ultrasound Guidance - A Multi-Center Study.

PubMed

Francica, Giampiero; Meloni, Maria Franca; de Sio, Ilario; Terracciano, Fulvia; Caturelli, Eugenio; Riccardi, Laura; Roselli, Paola; Iadevaia, Maddalena Diana; Scaglione, Mariano; Lenna, Giovanni; Chiang, Jason; Pompili, Maurizio

2017-12-12

Purpose  To retrospectively characterize the prevalence and impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for the biopsy of liver target lesions (LTLs) at six interventional ultrasound centers. Materials and Methods  The six participating centers retrospectively selected all patients in whom biopsy needles were positioned in LTLs during CEUS. The prevalence of CEUS-guided biopsies at each center between 2005 and 2016, contrast agent consumption, procedure indications, diagnostic yield and complications were assessed. Informed consent was obtained for all patients. Results  CEUS-guided biopsy of LTLs was carried out in 103 patients (68 M/35 F, median age: 69 yrs) with 103 liver target lesions (median size: 20 mm) using cutting needles (18 - 20 g) in 94 cases (91.2 %). CEUS-guided biopsy represented 2.6 % (range: 0.8 - 7.7 %) of 3818 biopsies on LTLs carried out at the participating centers. Indications to CEUS-guided biopsy were: a target lesion not visible on non-enhanced US (27.2 %), improvement of conspicuity of the target (33 %), choice of non-necrotic area inside the target (39.8 %). 26 patients (25.2 %) had a previously non-diagnostic cyto-histological exam. The diagnostic accuracy of the technique was 99 %. No major complications followed infusion of contrast agent or biopsy performance. Conclusion  The indications for CEUS-guided biopsy for LTLs are limited, but CEUS can be useful in challenging clinical scenarios, e. g. poorly visualized or invisible lesions or sampling of non-necrotic areas in the target lesions. There is also a potential advantage in using CEUS to guide repeat biopsies after unsuccessful sampling performed using the standard ultrasound technique. © Georg Thieme Verlag KG Stuttgart · New York.

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

PubMed Central

Nabili, Marjan; Geist, Craig; Zderic, Vesna

2015-01-01

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm2, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm2 (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nabili, Marjan, E-mail: mnabili@gwmail.gwu.edu; Geist, Craig, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu; Zderic, Vesna, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications ofmore » different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine

High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems.

PubMed

Ito, Koichi; Noro, Kazumasa; Yanagisawa, Yukari; Sakamoto, Maya; Mori, Shiro; Shiga, Kiyoto; Kodama, Tetsuya; Aoki, Takafumi

2015-12-01

An accurate method for detecting contrast agents using diagnostic ultrasound imaging systems is proposed. Contrast agents, such as microbubbles, passing through a blood vessel during ultrasound imaging are detected as blinking signals in the temporal axis, because their intensity value is constantly in motion. Ultrasound contrast agents are detected by evaluating the intensity variation of a pixel in the temporal axis. Conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject moves only slightly, a conventional detection method will introduce significant error. In contrast, the proposed technique employs spatiotemporal analysis of the pixel intensity variation over several frames. Experiments visualizing blood vessels in the mouse tail illustrated that the proposed method performs efficiently compared with conventional approaches. We also report that the new technique is useful for observing temporal changes in microvessel density in subiliac lymph nodes containing tumors. The results are compared with those of contrast-enhanced computed tomography. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Enhancement of cardiomyogenesis in stem cells by low intensity pulsed ultrasound

NASA Astrophysics Data System (ADS)

Teo, Ailing; Morshedi, Amir; Wang, Jen-Chieh; Lim, Mayasari; Zhou, Yufeng

2017-03-01

Low intensity pulsed ultrasound (LIPUS) has been shown to enhance bone and cartilage regeneration from stem cells. Gene expression of angiotensin II type 1 (AT1) receptor can be increased in LIPUS-treated osteoblasts. The AT1 receptor is a known mechanoreceptor in cardiomyocytes. It suggests that LIPUS may enhance cardiomyogenesis via mechanotransduction by increasing AT1 expression. Murine embryonic stem cells (ESCs) were treated daily by 10-min 1MHz LIPUS at spatial-average temporal-peak acoustic intensities of 30 mW/cm2 and 300 mW/cm2 in both continuous and pulsed wave (20% duty cycle) for 10 days. Polymerase chain reaction (PCR), immunocytochemistry, and beating rate were used to evaluate the cardiac viability quantitatively. After the treatment of LIPUS, beating rate of contractile areas and cardiac gene expression, such as α- and β-myosin heavy chain, were improved. Furthermore, no deleterious effects to the development of cardiac proteins were observed. All results suggest that LIPUS stimulation has the capacity of enhancing cardiomyogenesis from embryonic stem cells. With the benefit and the ease in incorporating LIPUS into various culture platforms, LIPUS has the potential to produce cardiomyocytes for clinical use in the future.

Role of Contrast-enhanced Ultrasound in the Evaluation of Inflammatory Arthritis

PubMed Central

Zhao, Chen-Yang; Jiang, Yu-Xin; Li, Jian-Chu; Xu, Zhong-Hui; Zhang, Qing; Su, Na; Yang, Meng

2017-01-01

Objective: Contrast-enhanced ultrasound (CEUS) is a well-established imaging modality which has been put into clinical use in recent years with the development of second-generation contrast agent and imaging devices, and its applications in the assessment of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, have provoked abundant discussion and researches among radiologists and rheumatologists. To summarize the achievements of clinical studies on CEUS in the application of arthritis, and to keep up with the latest progresses of the imaging technique, we reviewed the literature in recent years, hoping to establish the role of CEUS in joint diseases. Data Sources: PubMed and EMBASE. Study Selection: We searched the database with the conditions “contrast-enhanced ultrasound AND arthritis” with the time limitation of recent 10 years. Clinical studies applying CEUS in inflammatory arthritis and review articles about development of CEUS in joint diseases in English were selected. Results: As it is proved by most studies in recent years, by delineating microvasculature within the inflamed joints, CEUS can indicate early arthritis with high sensitivity and specificity. Moreover, the imaging of CEUS has been proved to be consistent with histopathological changes of inflammatory arthritis. Quantitative analysis of CEUS permits further evaluation of disease activity. CEUS also plays a significant role in the therapeutic monitoring of the disease, which has been backed up by a number of studies. Conclusions: CEUS may be a new choice for the rheumatologists to evaluate inflammatory arthritis, because of its low price, ability to provide dynamic pictures, and high sensitivity to angiogenesis. It can also be applied in disease classification and therapeutic monitoring. More studies about CEUS need to be done to set up the diagnostic standards. PMID:28685724

Effect of high intensity focused ultrasound (HIFU) in conjunction with a nanomedicines-microbubble complex for enhanced drug delivery.

PubMed

Han, Hyounkoo; Lee, Hohyeon; Kim, Kwangmeyung; Kim, Hyuncheol

2017-11-28

Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

PubMed

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

Enhanced ultrasound for advanced diagnostics, ultrasound tomography for volume limb imaging and prosthetic fitting

NASA Astrophysics Data System (ADS)

Anthony, Brian W.

2016-04-01

Ultrasound imaging methods hold the potential to deliver low-cost, high-resolution, operator-independent and nonionizing imaging systems - such systems couple appropriate algorithms with imaging devices and techniques. The increasing demands on general practitioners motivate us to develop more usable and productive diagnostic imaging equipment. Ultrasound, specifically freehand ultrasound, is a low cost and safe medical imaging technique. It doesn't expose a patient to ionizing radiation. Its safety and versatility make it very well suited for the increasing demands on general practitioners, or for providing improved medical care in rural regions or the developing world. However it typically suffers from sonographer variability; we will discuss techniques to address user variability. We also discuss our work to combine cylindrical scanning systems with state of the art inversion algorithms to deliver ultrasound systems for imaging and quantifying limbs in 3-D in vivo. Such systems have the potential to track the progression of limb health at a low cost and without radiation exposure, as well as, improve prosthetic socket fitting. Current methods of prosthetic socket fabrication remain subjective and ineffective at creating an interface to the human body that is both comfortable and functional. Though there has been recent success using methods like magnetic resonance imaging and biomechanical modeling, a low-cost, streamlined, and quantitative process for prosthetic cup design and fabrication has not been fully demonstrated. Medical ultrasonography may inform the design process of prosthetic sockets in a more objective manner. This keynote talk presents the results of progress in this area.

Ultrasound-assisted synthesis of poly(MMA-co-BA)/ZnO nanocomposites with enhanced physical properties.

PubMed

Poddar, Maneesh Kumar; Sharma, Sachin; Pattipaka, Srinivas; Pamu, D; Moholkar, Vijayanand S

2017-11-01

The present study reports synthesis and characterization of poly(MMA-co-BA)/ZnO nanocomposites using ultrasound-assisted in-situ emulsion polymerization. Methyl methacrylate (MMA) was copolymerized with butyl acrylate (BA), for enhanced ductility of copolymer matrix, in presence of nanoscale ZnO particles. Ultrasound generated strong micro-turbulence in reaction mixture, which resulted in higher encapsulation and uniform dispersion of ZnO (in native form - without surface modification) in polymer matrix, as compared to mechanical stirring. The nanocomposites were characterized for physical properties and structural morphology using standard techniques such as XRD, FTIR, particle size analysis, UV-Visible spectroscopy, electrical conductivity, TGA, DSC, FE-SEM and TEM. Copolymerization of MMA and BA (in presence of ZnO) followed second order kinetics. Thermal stability (T 10% =324.9°C) and glass transition temperature (T g =67.8°C) of poly(MMA-co-BA)/ZnO nanocomposites showed significant enhancement (35.1°C for 1wt% ZnO and 15.7°C for 4wt% ZnO, respectively), as compared to pristine poly(MMA-co-BA). poly(MMA-co-BA)/ZnO (5wt%) nanocomposites possessed the highest electrical conductivity of 0.192μS/cm and peak UV absorptivity of 0.55 at 372nm. Solution rheological study of nanocomposites revealed enhancement in viscosity with increasing ZnO loading. Maximum viscosity of 0.01Pa-s was obtained for 5wt% ZnO loading. Copyright © 2017 Elsevier B.V. All rights reserved.

Intravenous and Intracavitary Use of Contrast-Enhanced Ultrasound in the Evaluation and Management of Complicated Pediatric Pneumonia.

PubMed

Deganello, Annamaria; Rafailidis, Vasileios; Sellars, Maria E; Ntoulia, Aikaterini; Kalogerakou, Kleanthi; Ruiz, Gary; Cosgrove, David O; Sidhu, Paul S

2017-09-01

Pediatric pneumonia can be complicated by necrotizing pneumonia or a parapneumonic effusion either in the form of an empyema or a clear effusion. Ultrasonography (US) and computed tomography represent well-established modalities for evaluation of complicated pediatric pneumonia. Contrast-enhanced ultrasound (CEUS) was recently introduced and is gaining increasing acceptance in pediatric imaging. In this case series, we present our initial experience with both intravenous and intracavitary use of CEUS in children with complicated pneumonia. Intravenous CEUS accurately and confidently showed necrotizing pneumonia and delineated pleural effusions, whereas intracavitary CEUS accurately identified the chest catheter location and patency and showed the presence of loculations, suggesting the use of fibrinolytics. © 2017 by the American Institute of Ultrasound in Medicine.

A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor

NASA Astrophysics Data System (ADS)

Chen, Yu-Wei; Liu, Tse-Ying; Chang, Po-Hsueh; Hsu, Po-Hung; Liu, Hao-Li; Lin, Hong-Cheu; Chen, San-Yuan

2016-06-01

Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor.Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of

Mechanistic investigation in ultrasound induced enhancement of enzymatic hydrolysis of invasive biomass species.

PubMed

Borah, Arup Jyoti; Agarwal, Mayank; Poudyal, Manisha; Goyal, Arun; Moholkar, Vijayanand S

2016-08-01

This study has assessed four invasive weeds, viz. Saccharum spontaneum (SS), Mikania micrantha (MM), Lantana camara (LC) and Eichhornia crassipes (EC) for enzymatic hydrolysis prior to bioalcohol fermentation. Enzymatic hydrolysis of pretreated biomasses of weeds has been conducted with mechanical agitation and sonication under constant (non-optimum) conditions. Profiles of total reducible sugar release have been fitted to HCH-1 model of enzymatic hydrolysis using Genetic Algorithm. Trends in parameters of this model reveal physical mechanism of ultrasound-induced enhancement of enzymatic hydrolysis. Sonication accelerates hydrolysis kinetics by ∼10-fold. This effect is contributed by several causes, attributed to intense micro-convection generated during sonication: (1) increase in reaction velocity, (2) increase in enzyme-substrate affinity, (3) reduction in product inhibition, and (4) enhancement of enzyme activity due to conformational changes in its secondary structure. Enhancement effect of sonication is revealed to be independent of conditions of enzymatic hydrolysis - whether optimum or non-optimum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enzymolysis kinetics and structural characteristics of rice protein with energy-gathered ultrasound and ultrasound assisted alkali pretreatments.

PubMed

Li, Suyun; Yang, Xue; Zhang, Yanyan; Ma, Haile; Qu, Wenjuan; Ye, Xiaofei; Muatasim, Rahma; Oladejo, Ayobami Olayemi

2016-07-01

This research investigated the structural characteristics and enzymolysis kinetics of rice protein which was pretreated by energy-gathered ultrasound and ultrasound assisted alkali. The structural characteristics of rice protein before and after the pretreatment were performed with surface hydrophobicity and Fourier transform infrared (FTIR). There was an increase in the intensity of fluorescence spectrum and changes in functional groups after the pretreatment on rice protein compared with the control (without ultrasound and ultrasound assisted alkali processed), thus significantly enhancing efficiency of the enzymatic hydrolysis. A simplified kinetic equation for the enzymolysis model with the impeded reaction of enzyme was deduced to successfully describe the enzymatic hydrolysis of rice protein by different pretreatments. The initial observed rate constants (Kin,0) as well as ineffective coefficients (kimp) were proposed and obtained based on the experimental observation. The results showed that the parameter of kin,0 increased after ultrasound and ultrasound assisted alkali pretreatments, which proved the effects of the pretreatments on the substrate enhancing the enzymolysis process and had relation to the structure changes of the pretreatments on the substrate. Furthermore, the applicability of the simplified model was demonstrated by the enzymatic hydrolysis process for other materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Experiment on the factors for enhancing the susceptibility of cancer cells to chemotherapeutic drug by ultrasound microbubbles.

PubMed

Zhao, Ying-Zheng; Gao, Hui-Sheng; Zhou, Zhi-Cai; Tang, Qin-Qin; Lu, Cui-Tao; Jin, Zhuo; Tian, Ji-Lai; Xu, Yan-Yan; Tian, Xin-Qiao; Wang, Lee; Kong, Fan-Lei; Li, Xiao-Kun; Huang, Pin-Tong; He, Hui-Liao; Wu, Yan

2010-07-01

The objective of this study was to investigate the factors for enhancing the susceptibility of cancer cells to chemotherapeutic drug by ultrasound microbubbles. Ultrasound (US) combined with phospholipid-based microbubbles (MB) was used to enhance the susceptibility of colon cancer cell line SWD-620 to anticancer drugs Topotecan hydrochloride (TOP). Experiments were designed to investigate the influence of main factors on cell viability and cell inhibition, such as US intensity, MB concentration, drug combination with MB, asynchronous action between US triggered cavitation and drug entering cell, MB particle size. US exposure for 10 sec with US probe power at 0.6 W/cm(2) had satisfied cell viability. Treated with US combined with 15% MB, cell viability maintained more than 85% and cell inhibition 86.16%. Under optimal US combined with MB, TOP showed much higher cell inhibition than that of only TOP group. Cell inhibition under short delayed time (<2 h) for TOP addition did not show obvious difference. In terms of MB particle size, the order of cell inhibition was: Mixture > Micron bubble part > Nanometer bubble part. US combined with MB can enhance the susceptibility of cancer cells to chemotherapeutic drug, which may provide a potential method for US-mediated tumor chemotherapy.

Investigations into pulsed-high intensity focused ultrasound enhanced delivery: Preliminary evidence for a novel mechanism

PubMed Central

Hancock, Hilary A.; Smith, Lauren H.; Cuesta, Julian; Durrani, Amir K.; Angstadt, Mary; Palmeri, Mark L.; Kimmel, Eitan; Frenkel, Victor

2009-01-01

Pulsed-high intensity focused ultrasound (HIFU) exposures without ultrasound contrast agents have been used for non-invasively enhancing the delivery of various agents to improve their therapeutic efficacy in a variety of tissue models in a non-destructive manner. Despite the versatility of these exposures, little is known about the mechanisms by which their effects are produced. In this study pulsed-HIFU exposures were given in the flank muscle of mice, followed by the administration a variety of fluorophores, both soluble and particulate, by local or systemic injection. In vivo imaging (whole animal and microscopic) was used to quantify observations of increased extravasation and interstitial transport of the fluorophores as a result of the exposures. Histological analysis indicated that the exposures caused some structural alterations such as enlarged gaps between muscle fibers. These effects were consistent with increasing the permeability of the tissues; however they were found to be transient and reversed themselves gradually within 72 hrs. Simulations of radiation force induced displacements and the resulting local shear strain they produced were carried out to potentially explain the manner by which these effects occurred. A better understanding of the mechanisms involved with pulsed-HIFU exposures for non-invasively enhancing delivery will facilitate the process for optimizing their use. PMID:19616368

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

PubMed

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

PubMed

St Clair, Joshua R; Ramirez, David; Passman, Samantha; Benninger, Richard K P

2018-05-01

In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.

Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis

PubMed Central

Kim, Tae Kyoung; Jang, Hyun-Jung

2014-01-01

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis. CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography (CT) or magnetic resonance imaging (MRI) or as an initial diagnostic test for small newly detected liver nodules. CEUS has unique advantages over CT and MRI including no renal excretion of contrast, real-time imaging capability, and purely intravascular contrast. Hepatocellular carcinoma (HCC) is characterized by arterial-phase hypervascularity and later washout (negative enhancement). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase. However, there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout. Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rim-like or diffuse hypervascularity followed by rapid washout. Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS. CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance. CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC. PMID:24707142

Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis.

PubMed

Kim, Tae Kyoung; Jang, Hyun-Jung

2014-04-07

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis. CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography (CT) or magnetic resonance imaging (MRI) or as an initial diagnostic test for small newly detected liver nodules. CEUS has unique advantages over CT and MRI including no renal excretion of contrast, real-time imaging capability, and purely intravascular contrast. Hepatocellular carcinoma (HCC) is characterized by arterial-phase hypervascularity and later washout (negative enhancement). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase. However, there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout. Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rim-like or diffuse hypervascularity followed by rapid washout. Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS. CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance. CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.

Laser-enhanced high-intensity focused ultrasound heating in an in vivo small animal model

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2016-11-01

The enhanced heating effect during the combination of high-intensity focused ultrasound (HIFU) and low-optical-fluence laser illumination was investigated by using an in vivo murine animal model. The thighs of murine animals were synergistically irradiated by HIFU and pulsed nano-second laser light. The temperature increases in the target region were measured by a thermocouple under different HIFU pressures, which were 6.2, 7.9, and 9.8 MPa, in combination with 20 mJ/cm2 laser exposures at 532 nm wavelength. In comparison with conventional laser therapies, the laser fluence used here is at least one order of magnitude lower. The results showed that laser illumination could enhance temperature during HIFU applications. Additionally, cavitation activity was enhanced when laser and HIFU irradiation were concurrently used. Further, a theoretical simulation showed that the inertial cavitation threshold was indeed decreased when laser and HIFU irradiation were utilized concurrently.

[Effect of low-dose focused ultrasound pre-irradiation versus microbubbles for enhancing high-intensity focused ultrasound ablation of VX2 hepatic tumor in rabbits].

PubMed

Zhang, Yi; Yang, Chao; Zou, Jian-Zhong; Chen, Fei; Ou, Xia; Zou, Hai-Rong; Wang, Yan

2016-10-20

To compare the effect of low-dose focused ultrasound pre-irradiation and microbubbles for enhancing the ablation effect of high intensity focused ultrasound (HIFU) on VX 2 hepatic tumor in rabbits. Fifty-five rabbits bearing VX 2 hepatic tumor were randomly divided into low-dose pre-irradiation + HIFU ablation group, microbubbles+HIFU ablation group, and HIFU ablation group for corresponding treatments. The pathological changes in the tumors after low-dose irradiation, time for HIFU ablation, tumor volume with coagulative necrosis, energy efficiency factor (EEF), pathological changes in the ablated tumor, and sound channel of HIFU ablation were observed. Tumor cell edema, vacuolar changes in the cytoplasm and tumor interstitial vascular congestion were observed 24 h after low-dose pre-irradiation. The ablation time were significantly shorter, coagulative necrosis volume was larger, and EEF was lower in low-dose irradiation + HIFU ablation group and microbubbles+HIFU ablation group than in simple HIFU ablation group (P<0.05), but the differences between the former two groups were not significant. The effectiveness and stability of the synergistic effect of low-dose pre-irradiation were inferior to microbubbles, but the former ensured a better safety of the sound channel. Low-dose irradiation has comparable synergistic effect in HIFU with microbubbles with such advantages as non-invasiveness, high concentration and good safety, and can be a potentially new method to enhance the efficiency of HIFU.

[Novel dianostics and therapeutics with ultrasound technologies and nanotechnologies].

PubMed

Suzuki, Ryo; Oda, Yusuke; Omata, Daiki; Sawaguchi, Yoshikazu; Negishi, Yoichi; Maruyama, Kazuo

2013-01-01

Ultrasound is a good tool for theranostics due to have multi-potency both of diagnostics with sonography and therapeutics with high intensity focused ultrasound (HIFU). In addition, microbubbles and nanobubbles are utilized as not only contrast imaging agent but also enhancer of drug and gene delivery by combination of ultrasound. Recently, we developed novel liposomal nanobubbles (Bubble liposomes) which were containing perfluoropropane. Bubble liposomes induced jet stream by low intensity ultrasound exposure and resulted in enhancing permeability of cell membrane. This phenomenon has been utilized as driving force for drug and gene delivery. On the other hand, the combination of Bubble liposomes and high intensity ultrasound induces strong jet stream and increase temperature. This condition can directly damage to tumor cells, we are applying this for cancer therapy. Therefore, their combination has potency for various cancer therapies such as gene therapy, immunotherapy and hyperthermia. In this review, we discuss about cancer therapy by the combination of Bubble liposomes and ultrasound.

Towards Dynamic Contrast Specific Ultrasound Tomography

NASA Astrophysics Data System (ADS)

Demi, Libertario; van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo

2016-10-01

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

Towards Dynamic Contrast Specific Ultrasound Tomography.

PubMed

Demi, Libertario; Van Sloun, Ruud J G; Wijkstra, Hessel; Mischi, Massimo

2016-10-05

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

Towards Dynamic Contrast Specific Ultrasound Tomography

PubMed Central

Demi, Libertario; Van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo

2016-01-01

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast. PMID:27703251

Improved heating efficiency with High-Intensity Focused Ultrasound using a new ultrasound source excitation.

PubMed

Bigelow, Timothy A

2009-01-01

High-Intensity Focused Ultrasound (HIFU) is quickly becoming one of the best methods to thermally ablate tissue noninvasively. Unlike RF or Laser ablation, the tissue can be destroyed without inserting any probes into the body minimizing the risk of secondary complications such as infections. In this study, the heating efficiency of HIFU sources is improved by altering the excitation of the ultrasound source to take advantage of nonlinear propagation. For ultrasound, the phase velocity of the ultrasound wave depends on the amplitude of the wave resulting in the generation of higher harmonics. These higher harmonics are more efficiently converted into heat in the body due to the frequency dependence of the ultrasound absorption in tissue. In our study, the generation of the higher harmonics by nonlinear propagation is enhanced by transmitting an ultrasound wave with both the fundamental and a higher harmonic component included. Computer simulations demonstrated up to a 300% increase in temperature increase compared to transmitting at only the fundamental for the same acoustic power transmitted by the source.

Towards ultrasound enhanced mid-IR spectroscopy for sensing bacteria in aqueous solutions

NASA Astrophysics Data System (ADS)

Freitag, Stephan; Schwaighofer, Andreas; Radel, Stefan; Lendl, Bernhard

2018-02-01

We employ attenuated total reflection (ATR) mid-IR technology for sensing of bacteria present in aqueous solution. In ATR spectroscopy, the penetration depth of the evanescent field extends to approx. 1-2 micrometers into the aqueous solution depending on the refractive index of the employed materials (Si, ZnS, Ge) used as attenuated total reflection (ATR) element and the geometry of the optical set-up. Due to the flow profile in the microfluidic cell, an additional force is required to bring particles into the evanescent field for measurement. For that purpose, we employ standing ultrasound waves produced between a sound source vibrating at approx. 2 MHz and the ATR crystal acting as a reflector. This ultrasonic trap is integrated into the microfluidic channel. As aqueous solution is passing through that acoustofluidic cell, particles are concentrated in the nodal plane of the standing ultrasound wave, forming particle conglomerates. By selecting appropriate experimental conditions, it is then possible to press bacteria against the crystal surface for interaction with the evanescent wave (as well as to keep them away from the ATR element). Our current work aims at establishing a custommade US-ATR-IR setup for signal enhancement of bacteria (e.g. E. coli, P. aeruginosa as well as Salmonella) in drinking water.

Microalgae as feedstock for biodiesel production under ultrasound treatment - A review.

PubMed

Sivaramakrishnan, Ramachandran; Incharoensakdi, Aran

2018-02-01

The application of ultrasound in biodiesel production has recently emerged as a novel technology. Ultrasound treatment enhances the mass transfer characteristics leading to the increased reaction rate with short reaction time and potentially reduces the production cost. In this review, application of ultrasound-assisted biodiesel production using acid, base and enzyme catalysts is presented. A critical assessment of the current status of ultrasound in biodiesel production was discussed with the emphasis on using ultrasound for efficient microalgae biodiesel production. The ultrasound in the biodiesel production enhances the emulsification of immiscible liquid reactant by microturbulence generated by cavitation bubbles. The major benefit of the ultrasound-assisted biodiesel production is a reduction in reaction time. Several different methods have been discussed to improve the biodiesel production. Overall, this review focuses on the current understanding of the application of ultrasound in biodiesel production from microalgae and to provide insights into future developments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultrasound mediated nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Mullin, Lee B.

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

Duration of ultrasound-mediated enhanced plasma membrane permeability.

PubMed

Lammertink, Bart; Deckers, Roel; Storm, Gert; Moonen, Chrit; Bos, Clemens

2015-03-30

Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2 h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3 h after sonication. Copyright © 2014 Elsevier B.V. All rights reserved.

Technical aspects of contrast-enhanced ultrasound (CEUS) examinations: tips and tricks.

PubMed

Greis, C

2014-01-01

Ultrasound contrast agents have substantially extended the clinical value of ultrasound, allowing the assessment of blood flow and distribution in real-time down to microcapillary level. Selective imaging of contrast agent signals requires a contrast-specific imaging mode on the ultrasound scanner, allowing real-time separation of tissue and contrast agent signals. The creation of a contrast image requires a specific interaction between the insonated ultrasound wave and the contrast agent microbubbles, leading to persistent oscillation of the bubbles. Several technical and procedural parameters have a significant influence on the quality of CEUS images and should be controlled carefully to obtain good image quality and a reliable diagnosis. Achieving the proper balance between the respective parameters is a matter of technical knowledge and experience. Appropriate training and education should be mandatory for every investigator performing CEUS examinations.

Focusing of ferroelectret air-coupled ultrasound transducers

NASA Astrophysics Data System (ADS)

Gaal, Mate; Bartusch, Jürgen; Dohse, Elmar; Schadow, Florian; Köppe, Enrico

2016-02-01

Air-coupled ultrasound has been applied increasingly as a non-destructive testing method for lightweight construction in recent years. It is particularly appropriate for composite materials being used in automotive and aviation industry. Air-coupled ultrasound transducers mostly consist of piezoelectric materials and matching layers. However, their fabrication is challenging and their signal-to-noise ratio often not sufficient for many testing requirements. To enhance the efficiency, air-coupled ultrasound transducers made of cellular polypropylene have been developed. Because of its small density and sound velocity, this piezoelectric ferroelectret matches the small acoustic impedance of air much better than matching layers applied in conventional transducers. In our contribution, we present two different methods of spherical focusing of ferroelectret transducers for the further enhancement of their performance in NDT applications. Measurements on carbon-fiber-reinforced polymer (CFRP) samples and on metal adhesive joints performed with commercially available focused air-coupled ultrasound transducers are compared to measurements executed with self-developed focused ferroelectret transducers.

International guidelines for contrast-enhanced ultrasonography: ultrasound imaging in the new millennium

PubMed Central

Lorentzen, Torben

2016-01-01

The intent of this review is to discuss and comment on common clinical scenarios in which contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity. PMID:26867761

Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability

PubMed Central

Tang, M.-X.; Mulvana, H.; Gauthier, T.; Lim, A. K. P.; Cosgrove, D. O.; Eckersley, R. J.; Stride, E.

2011-01-01

Ultrasound provides a valuable tool for medical diagnosis offering real-time imaging with excellent spatial resolution and low cost. The advent of microbubble contrast agents has provided the additional ability to obtain essential quantitative information relating to tissue vascularity, tissue perfusion and even endothelial wall function. This technique has shown great promise for diagnosis and monitoring in a wide range of clinical conditions such as cardiovascular diseases and cancer, with considerable potential benefits in terms of patient care. A key challenge of this technique, however, is the existence of significant variations in the imaging results, and the lack of understanding regarding their origin. The aim of this paper is to review the potential sources of variability in the quantification of tissue perfusion based on microbubble contrast-enhanced ultrasound images. These are divided into the following three categories: (i) factors relating to the scanner setting, which include transmission power, transmission focal depth, dynamic range, signal gain and transmission frequency, (ii) factors relating to the patient, which include body physical differences, physiological interaction of body with bubbles, propagation and attenuation through tissue, and tissue motion, and (iii) factors relating to the microbubbles, which include the type of bubbles and their stability, preparation and injection and dosage. It has been shown that the factors in all the three categories can significantly affect the imaging results and contribute to the variations observed. How these factors influence quantitative imaging is explained and possible methods for reducing such variations are discussed. PMID:22866229

Enhancement of drying and rehydration characteristics of okra by ultrasound pre-treatment application

NASA Astrophysics Data System (ADS)

Tüfekçi, Senem; Özkal, Sami Gökhan

2017-07-01

Effect of ultrasound application prior to hot air drying on drying and rehydration kinetics, rehydration ratio and microstructure of okra slices were investigated. For this purpose, the selected parameters are ultrasound pre-treatment time (10, 20 and 30 min), ultrasound amplitude (55 and 100%) and the temperature of drying air (60 and 70 °C). 5 mm thick cylindrical shaped okra slices were used in the experiments. The samples were immersed in water and ultrasonic pre-treatments were done in water with ultrasonic probe connected to an ultrasonic generator with 20 kHz frequency. Pre-treated samples were dried in a tray drier with a 0.3 m/s air velocity. Ultrasound pre-treatment affected the drying rate of the okra slices significantly. Drying time of okra slices was decreased by the application of ultrasound pre-treatment. Modified Page model found to be the most suitable model for describing the drying characteristics of okra slices. Improvements in rehydration properties of the dried samples were observed due to the ultrasound pre-treatment. The influence of the ultrasound pre-treatment on microstructure was clearly observed through scanning electron microscopy images of the dried samples. As the amplitude of ultrasound increased the changes in structure of the okra tissue increased.

Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in inflammatory bowel disease patients: a pilot study.

PubMed

Goertz, Ruediger S; Klett, Daniel; Wildner, Dane; Atreya, Raja; Neurath, Markus F; Strobel, Deike

2018-01-01

Background Microvascularization of the bowel wall can be visualized and quantified non-invasively by software-assisted analysis of derived time-intensity curves. Purpose To perform software-based quantification of bowel wall perfusion using quantitative contrast-enhanced ultrasound (CEUS) according to clinical response in patients with inflammatory bowel disease treated with vedolizumab. Material and Methods In a prospective study, in 18 out of 34 patients, high-frequency ultrasound of bowel wall thickness using color Doppler flow combined with CEUS was performed at baseline and after 14 weeks of treatment with vedolizumab. Clinical activity scores at week 14 were used to differentiate between responders and non-responders. CEUS parameters were calculated by software analysis of the video loops. Results Nine of 18 patients (11 with Crohn's disease and seven with ulcerative colitis) showed response to treatment with vedolizumab. Overall, the responder group showed a significant decrease in the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS parameters of mural microvascularization such as peak enhancement or wash-in rate decreased in responders, in contrast with non-responders. Time-derived parameters remained stable or increased during treatment in all patients. Conclusion Analysis of bowel microvascularization by CEUS shows statistically significant changes in the wash-in-rate related to response of vedolizumab therapy.

Correction of Non-Linear Propagation Artifact in Contrast-Enhanced Ultrasound Imaging of Carotid Arteries: Methods and in Vitro Evaluation.

PubMed

Yildiz, Yesna O; Eckersley, Robert J; Senior, Roxy; Lim, Adrian K P; Cosgrove, David; Tang, Meng-Xing

2015-07-01

Non-linear propagation of ultrasound creates artifacts in contrast-enhanced ultrasound images that significantly affect both qualitative and quantitative assessments of tissue perfusion. This article describes the development and evaluation of a new algorithm to correct for this artifact. The correction is a post-processing method that estimates and removes non-linear artifact in the contrast-specific image using the simultaneously acquired B-mode image data. The method is evaluated on carotid artery flow phantoms with large and small vessels containing microbubbles of various concentrations at different acoustic pressures. The algorithm significantly reduces non-linear artifacts while maintaining the contrast signal from bubbles to increase the contrast-to-tissue ratio by up to 11 dB. Contrast signal from a small vessel 600 μm in diameter buried in tissue artifacts before correction was recovered after the correction. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

PubMed Central

Zhang, Man; Fabiilli, Mario L.; Haworth, Kevin J.; Padilla, Frederic; Swanson, Scott D.; Kripfgans, Oliver D.; Carson, Paul L.; Fowlkes, J. Brian

2011-01-01

Rationale and Objectives Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. Our hypothesis was that microbubbles generated by ADV could enhance high intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption. Materials and Methods Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W·cm-2 in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted MRI. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup. Results Thermal lesions were seven-fold larger in phantoms containing droplets (3×105 droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2 s HIFU exposure in droplet-containing phantoms was comparable to that made by a 5 s exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm3 (n = 4, 5 s exposure) and 0.265 ± 0.005 cm3 (n = 3, 5 s exposure), respectively – a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by MRI. Conclusion ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power, and provide ultrasonic imaging feedback of the thermal therapy. PMID:21703883

Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging

PubMed Central

Martin, K. Heath; Lindsey, Brooks D.; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F. Stuart; Jiang, Xiaoning; Dayton, Paul A.

2014-01-01

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed. PMID:25375755

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

PubMed

Martin, K Heath; Lindsey, Brooks D; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F Stuart; Jiang, Xiaoning; Dayton, Paul A

2014-11-04

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

Varying ultrasound power level to distinguish surgical instruments and tissue.

PubMed

Ren, Hongliang; Anuraj, Banani; Dupont, Pierre E

2018-03-01

We investigate a new framework of surgical instrument detection based on power-varying ultrasound images with simple and efficient pixel-wise intensity processing. Without using complicated feature extraction methods, we identified the instrument with an estimated optimal power level and by comparing pixel values of varying transducer power level images. The proposed framework exploits the physics of ultrasound imaging system by varying the transducer power level to effectively distinguish metallic surgical instruments from tissue. This power-varying image-guidance is motivated from our observations that ultrasound imaging at different power levels exhibit different contrast enhancement capabilities between tissue and instruments in ultrasound-guided robotic beating-heart surgery. Using lower transducer power levels (ranging from 40 to 75% of the rated lowest ultrasound power levels of the two tested ultrasound scanners) can effectively suppress the strong imaging artifacts from metallic instruments and thus, can be utilized together with the images from normal transducer power levels to enhance the separability between instrument and tissue, improving intraoperative instrument tracking accuracy from the acquired noisy ultrasound volumetric images. We performed experiments in phantoms and ex vivo hearts in water tank environments. The proposed multi-level power-varying ultrasound imaging approach can identify robotic instruments of high acoustic impedance from low-signal-to-noise-ratio ultrasound images by power adjustments.

MR-guided transcranial focused ultrasound safely enhances interstitial dispersion of large polymeric nanoparticles in the living brain

PubMed Central

Mohammadabadi, Ali; Nguyen, Ben A.; Guo, Sijia; Winkles, Jeffrey A.; Kim, Anthony J.; Gullapalli, Rao; Keller, Asaf; Frenkel, Victor

2018-01-01

Generating spatially controlled, non-destructive changes in the interstitial spaces of the brain has a host of potential clinical applications, including enhancing the delivery of therapeutics, modulating biological features within the tissue microenvironment, altering fluid and pressure dynamics, and increasing the clearance of toxins, such as plaques found in Alzheimer’s disease. Recently we demonstrated that ultrasound can non-destructively enlarge the interstitial spaces of the brain ex vivo. The goal of the current study was to determine whether these effects could be reproduced in the living brain using non-invasive, transcranial MRI-guided focused ultrasound (MRgFUS). The left striatum of healthy rats was treated using MRgFUS. Computer simulations facilitated treatment planning, and targeting was validated using MRI acoustic radiation force impulse imaging. Following MRgFUS treatments, Evans blue dye or nanoparticle probes were infused to assess changes in the interstitial space. In MRgFUS-treated animals, enhanced dispersion was observed compared to controls for 70 nm (12.8 ± 0.9 mm3 vs. 10.6 ± 1.0 mm3, p = 0.01), 200 nm (10.9 ± 1.4 mm3 vs. 7.4 ± 0.7 mm3, p = 0.01) and 700 nm (7.5 ± 0.4 mm3 vs. 5.4 ± 1.2 mm3, p = 0.02) nanoparticles, indicating enlargement of the interstitial spaces. No evidence of significant histological or electrophysiological injury was identified. These findings suggest that transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses. This has the potential to expand the therapeutic uses of MRgFUS. PMID:29415084

Real-time sound speed correction using golden section search to enhance ultrasound imaging quality

NASA Astrophysics Data System (ADS)

Yoon, Chong Ook; Yoon, Changhan; Yoo, Yangmo; Song, Tai-Kyong; Chang, Jin Ho

2013-03-01

In medical ultrasound imaging, high-performance beamforming is important to enhance spatial and contrast resolutions. A modern receive dynamic beamfomer uses a constant sound speed that is typically assumed to 1540 m/s in generating receive focusing delays [1], [2]. However, this assumption leads to degradation of spatial and contrast resolutions particularly when imaging obese patients or breast since the sound speed is significantly lower than the assumed sound speed [3]; the true sound speed in the fatty tissue is around 1450 m/s. In our previous study, it was demonstrated that the modified nonlinear anisotropic diffusion is capable of determining an optimal sound speed and the proposed method is a useful tool to improve ultrasound image quality [4], [5]. In the previous study, however, we utilized at least 21 iterations to find an optimal sound speed, which may not be viable for real-time applications. In this paper, we demonstrates that the number of iterations can be dramatically reduced using the GSS(golden section search) method with a minimal error. To evaluate performances of the proposed method, in vitro experiments were conducted with a tissue mimicking phantom. To emulate a heterogeneous medium, the phantom was immersed in the water. From the experiments, the number of iterations was reduced from 21 to 7 with GSS method and the maximum error of the lateral resolution between direct and GSS was less than 1%. These results indicate that the proposed method can be implemented in real time to improve the image quality in the medical ultrasound imaging.

Assessment of ultrasound modulation of near infrared light on the quantification of scattering coefficient.

PubMed

Singh, M Suheshkumar; Yalavarthy, Phaneendra K; Vasu, R M; Rajan, K

2010-07-01

To assess the effect of ultrasound modulation of near infrared (NIR) light on the quantification of scattering coefficient in tissue-mimicking biological phantoms. A unique method to estimate the phase of the modulated NIR light making use of only time averaged intensity measurements using a charge coupled device camera is used in this investigation. These experimental measurements from tissue-mimicking biological phantoms are used to estimate the differential pathlength, in turn leading to estimation of optical scattering coefficient. A Monte-Carlo model based numerical estimation of phase in lieu of ultrasound modulation is performed to verify the experimental results. The results indicate that the ultrasound modulation of NIR light enhances the effective scattering coefficient. The observed effective scattering coefficient enhancement in tissue-mimicking viscoelastic phantoms increases with increasing ultrasound drive voltage. The same trend is noticed as the ultrasound modulation frequency approaches the natural vibration frequency of the phantom material. The contrast enhancement is less for the stiffer (larger storage modulus) tissue, mimicking tumor necrotic core, compared to the normal tissue. The ultrasound modulation of the insonified region leads to an increase in the effective number of scattering events experienced by NIR light, increasing the measured phase, causing the enhancement in the effective scattering coefficient. The ultrasound modulation of NIR light could provide better estimation of scattering coefficient. The observed local enhancement of the effective scattering coefficient, in the ultrasound focal region, is validated using both experimental measurements and Monte-Carlo simulations.

Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound

PubMed Central

Xu, H-X; Lu, M-D; Liu, L-N; Zhang, Y-F; Guo, L-H; Xu, J-M; Liu, C

2012-01-01

Objectives To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound. Methods A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20–82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent. Results Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1–3.0 cm and 3.1–5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1–3.0 cm and 3.1–5.0 cm in diameter. Conclusions CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation. PMID:22553290

Intravascular ultrasound catheter to enhance microbubble-based drug delivery via acoustic radiation force.

PubMed

Kilroy, Joseph P; Klibanov, Alexander L; Wamhoff, Brian R; Hossack, John A

2012-10-01

Previous research has demonstrated that acoustic radiation force enhances intravascular microbubble adhesion to blood vessels in the presence of flow for moleculartargeted ultrasound imaging and drug delivery. A prototype acoustic radiation force intravascular ultrasound (ARFIVUS) catheter was designed and fabricated to displace a microbubble contrast agent in flow representative of conditions encountered in the human carotid artery. The prototype ARFIVUS transducer was designed to match the resonance frequency of 1.4- to 2.6-μm-diameter microbubbles modeled by an experimentally verified 1-D microbubble acoustic radiation force translation model. The transducer element was an elongated Navy Type I (hard) lead zirconate titanate (PZT) ceramic designed to operate at 3 MHz. Fabricated devices operated with center frequencies of 3.3 and 3.6 MHz with -6-dB fractional bandwidths of 55% and 50%, respectively. Microbubble translation velocities as high as 0.86 m/s were measured using a high-speed streak camera when insonating with the ARFIVUS transducer. Finally, the prototype was used to displace microbubbles in a flow phantom while imaging with a commercial 45-MHz imaging IVUS transducer. A sustained increase of 31 dB in average video intensity was measured following insonation with the ARFIVUS, indicating microbubble accumulation resulting from the application of acoustic radiation force.

Control of treatment size in cavitation-enhanced high-intensity focused ultrasound using radio-frequency echo signals

NASA Astrophysics Data System (ADS)

Tomiyasu, Kentaro; Takagi, Ryo; Iwasaki, Ryosuke; Yoshizawa, Shin; Umemura, Shin-ichiro

2017-07-01

In high-intensity focused ultrasound (HIFU) treatment, controlling the ultrasound dose at each focal target spot is important because it is a problem that the length of the coagulated region in front of the focal point deviates owing to the differences in absorption in each focal target spot and attenuation in the intervening tissues. In this study, the detected changes in the power spectra of HIFU echoes were used by controlling the HIFU duration in the “trigger HIFU” sequence with the aim to increase coagulation size through the enhancement of the ultrasonic heating by the cavitation induced by the preceding extremely high intensity short “trigger” pulse. The result shows that this method can be used to detect boiling bubbles and the following generated cavitation bubbles at their early stage. By automatically stopping HIFU exposure immediately after detecting the bubbles, overheating was prevented and the deviation of the length of the coagulated region was reduced.

Development of therapeutic microbubbles for enhancing ultrasound-mediated gene delivery.

PubMed

Sun, Ryan R; Noble, Misty L; Sun, Samuel S; Song, Shuxian; Miao, Carol H

2014-05-28

Ultrasound (US)-mediated gene delivery has emerged as a promising non-viral method for safe and selective gene delivery. When enhanced by the cavitation of microbubbles (MBs), US exposure can induce sonoporation that transiently increases cell membrane permeability for localized delivery of DNA. The present study explores the effect of generalizable MB customizations on MB facilitation of gene transfer compared to Definity®, a clinically available contrast agent. These modifications are 1) increased MB shell acyl chain length (RN18) for elevated stability and 2) addition of positive charge on MB (RC5K) for greater DNA associability. The MB types were compared in their ability to facilitate transfection of luciferase and GFP reporter plasmid DNA in vitro and in vivo under various conditions of US intensity, MB dosage, and pretreatment MB-DNA incubation. The results indicated that both RN18 and RC5K were more efficient than Definity®, and that the cationic RC5K can induce even greater transgene expression by increasing payload capacity with prior DNA incubation without compromising cell viability. These findings could be applied to enhance MB functions in a wide range of therapeutic US/MB gene and drug delivery approach. With further designs, MB customizations have the potential to advance this technology closer to clinical application. Copyright © 2014 Elsevier B.V. All rights reserved.

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

PubMed

Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

2016-02-01

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Gold nanoparticle nucleated cavitation for enhanced high intensity focused ultrasound therapy

NASA Astrophysics Data System (ADS)

McLaughlan, J. R.; Cowell, D. M. J.; Freear, S.

2018-01-01

High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5-35 dB for peak negative pressures between 1.19-3.19  ±  0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2-2.71  ±  0.01 MPa at a fluence of 3.4 mJ cm-2 . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of 1.5 × 103 a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as

Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound.

PubMed

Kalantarinia, Kambiz; Belcik, J Todd; Patrie, James T; Wei, Kevin

2009-10-01

Current methods for measuring renal blood flow (RBF) are time consuming and not widely available. Contrast-enhanced ultrasound (CEU) is a safe and noninvasive imaging technique suitable for assessment of tissue blood flow, which has been used clinically to assess myocardial blood flow. We tested the utility of CEU in monitoring changes in RBF in healthy volunteers. We utilized CEU to monitor the expected increase in RBF following a high protein meal in healthy adults. Renal cortical perfusion was assessed by CEU using low mechanical index (MI) power modulation Angio during continuous infusions of Definity. Following destruction of tissue microbubbles using ultrasound at a MI of 1.0, the rate of tissue replenishment with microbubbles and the plateau acoustic intensity (AI) were used to estimate the RBF velocity and cortical blood volume, respectively. Healthy adults (n = 19, mean age 26.6 yr) were enrolled. The A.beta parameter of CEU, representing mean RBF increased by 42.8%from a baseline of 17.05 +/- 6.23 to 23.60 +/- 6.76 dB/s 2 h after the ingestion of the high-protein meal (P = 0.002). Similarly, there was a 37.3%increase in the beta parameter, representing the geometric mean of blood velocity after the high protein meal (P < 0.001). The change in cortical blood volume was not significant (P = 0.89). Infusion time of Definity was 6.3 +/- 2.0 min. The ultrasound contrast agent was tolerated well with no serious adverse events. CEU is a fast, noninvasive, and practical imaging technique that may be useful for monitoring renal blood velocity, volume, and flow.

Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies

PubMed Central

Arvanitis, Costas D.; McDannold, Nathan

2013-01-01

Purpose: Ultrasound can be used to noninvasively produce different bioeffects via viscous heating, acoustic cavitation, or their combination, and these effects can be exploited to develop a wide range of therapies for cancer and other disorders. In order to accurately localize and control these different effects, imaging methods are desired that can map both temperature changes and cavitation activity. To address these needs, the authors integrated an ultrasound imaging array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously visualize thermal and mechanical effects via passive acoustic mapping (PAM) and MR temperature imaging (MRTI), respectively. Methods: The system was tested with an MRgFUS system developed for transcranial sonication for brain tumor ablation in experiments with a tissue mimicking phantom and a phantom-filled ex vivo macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous wave sonications were applied at increasing power levels (30–110 W) until broadband acoustic emissions (a signature for inertial cavitation) were evident. The presence or lack of signal in the PAM, as well as its magnitude and location, were compared to the focal heating in the MRTI. Additional experiments compared PAM with standard B-mode ultrasound imaging and tested the feasibility of the system to map cavitation activity produced during low-power (5 W) burst sonications in a channel filled with a microbubble ultrasound contrast agent. Results: When inertial cavitation was evident, localized activity was present in PAM and a marked increase in heating was observed in MRTI. The location of the cavitation activity and heating agreed on average after registration of the two imaging modalities; the distance between the maximum cavitation activity and focal heating was −3.4 ± 2.1 mm and −0.1 ± 3.3 mm in the axial and transverse ultrasound array directions, respectively. Distortions and other MRI issues introduced small

Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies.

PubMed

Arvanitis, Costas D; McDannold, Nathan

2013-11-01

Ultrasound can be used to noninvasively produce different bioeffects via viscous heating, acoustic cavitation, or their combination, and these effects can be exploited to develop a wide range of therapies for cancer and other disorders. In order to accurately localize and control these different effects, imaging methods are desired that can map both temperature changes and cavitation activity. To address these needs, the authors integrated an ultrasound imaging array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously visualize thermal and mechanical effects via passive acoustic mapping (PAM) and MR temperature imaging (MRTI), respectively. The system was tested with an MRgFUS system developed for transcranial sonication for brain tumor ablation in experiments with a tissue mimicking phantom and a phantom-filled ex vivo macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous wave sonications were applied at increasing power levels (30-110 W) until broadband acoustic emissions (a signature for inertial cavitation) were evident. The presence or lack of signal in the PAM, as well as its magnitude and location, were compared to the focal heating in the MRTI. Additional experiments compared PAM with standard B-mode ultrasound imaging and tested the feasibility of the system to map cavitation activity produced during low-power (5 W) burst sonications in a channel filled with a microbubble ultrasound contrast agent. When inertial cavitation was evident, localized activity was present in PAM and a marked increase in heating was observed in MRTI. The location of the cavitation activity and heating agreed on average after registration of the two imaging modalities; the distance between the maximum cavitation activity and focal heating was -3.4 ± 2.1 mm and -0.1 ± 3.3 mm in the axial and transverse ultrasound array directions, respectively. Distortions and other MRI issues introduced small uncertainties in the PAM�

Advanced Ultrasound Technologies for Diagnosis and Therapy.

PubMed

Rix, Anne; Lederle, Wiltrud; Theek, Benjamin; Lammers, Twan; Moonen, Chrit; Schmitz, Georg; Kiessling, Fabian

2018-05-01

Ultrasound is among the most rapidly advancing imaging techniques. Functional methods such as elastography have been clinically introduced, and tissue characterization is improved by contrast-enhanced scans. Here, novel superresolution techniques provide unique morphologic and functional insights into tissue vascularization. Functional analyses are complemented by molecular ultrasound imaging, to visualize markers of inflammation and angiogenesis. The full potential of diagnostic ultrasound may become apparent by integrating these multiple imaging features in radiomics approaches. Emerging interest in ultrasound also results from its therapeutic potential. Various applications of tumor ablation with high-intensity focused ultrasound are being clinically evaluated, and its performance strongly benefits from the integration into MRI. Additionally, oscillating microbubbles mediate sonoporation to open biologic barriers, thus improving the delivery of drugs or nucleic acids that are coadministered or coformulated with microbubbles. This article provides an overview of recent developments in diagnostic and therapeutic ultrasound, highlighting multiple innovation tracks and their translational potential. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Villous adenoma of the common hepatic duct: the importance of contrast-enhanced ultrasound and endoscopic retrograde cholangiopancreatography for relevant diagnosis. A case report and review of the literature.

PubMed

Tefas, Cristian; Tanţău, Marcel; Szenftleben, Alexandru; Chiorean, Liliana; Badea, Radu

2015-12-01

Adenomas are frequently encountered in the lower digestive tract but are rarely diagnosed in the biliary tree. We report a case of villous adenoma of the common hepatic duct. A 58-year old male was admitted with a four week history of intermittent upper right quadrant pain. Gray scale and contrast-enhanced abdominal ultrasound showed a mass inside the common hepatic duct with arterial enhancement and slow wash-out during the late venous phase. Subsequent endoscopic retrograde cholangiopancreatography and intraductal ultrasound confirmed the presence of the lesion. The final histopathological examination showed villous adenoma of the common hepatic duct with high-grade dysplasia. Contrast enhanced ultrasonography used in conjecture with endoscopic retrograde cholangiopancreatography can help in differentiating biliary tumors.

An Algorithm of Image Heterogeneity with Contrast-Enhanced Ultrasound in Differential Diagnosis of Solid Thyroid Nodules.

PubMed

Jin, Lifang; Xu, Changsong; Xie, Xueqian; Li, Fan; Lv, Xiuhong; Du, Lianfang

2017-01-01

Enhancement heterogeneity on contrast-enhanced ultrasonography (CEUS) is used to differentiate between benign and malignant thyroid nodules. In this study, we used an algorithm to quantify enhancement heterogeneity of solid thyroid nodules on CEUS. The heterogeneity value (HV) is calculated as standard deviation/mean intensity × 100 (using Adobe Photoshop). The heterogeneity ratio (HR) is calculated as the ratio of the HV of the nodule to that of the surrounding parenchyma. Three phases-ascending, peak and descending phases-were studied. HV values at ascending (HV a ) and peak (HV p ) phases were significantly higher in malignant nodules than in benign nodules (95.57 ± 43.87 vs. 73.06 ± 44.04, p = 0.009, and 32.53 ± 10.73 vs. 26.44 ± 8.25, p = 0.002, respectively). HR a , HR p and HR d were significantly higher in malignant nodules than in benign nodules (1.93 ± 1.03 vs. 1.00 ± 0.47, p = 0.000, 1.43 ± 0.51 vs. 1.09 ± 0.28, p = 0.000, and 1.33 ± 0.40 vs. 1.08 ± 0.33, p = 0.001, respectively). HR a achieved optimal diagnostic performance on receiver operating characteristic curve analysis. The algorithm used for assessment of image heterogeneity on CEUS examination may be a useful adjunct to conventional ultrasound for differential diagnosis of solid thyroid nodules. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

PubMed

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Enhancement of Cell Ingrowth, Proliferation, and Early Differentiation in a Three-Dimensional Silicon Carbide Scaffold Using Low-Intensity Pulsed Ultrasound

PubMed Central

Lin, Liangjun

2015-01-01

the sham control group, respectively. Alkaline phosphatase activity was significantly increased by the treatment of ultrasound at 4 (p=0.012) and 7 days (p=0.035). These results suggested that ultrasound treatment with low-intensity acoustic energy facilitated the cellular ingrowth and enhanced the proliferation and early differentiation of osteoblasts in SiC scaffolds. PMID:24935158

Ultrasound and Perforated Viscus; Dirty Fluid, Dirty Shadows, and Peritoneal Enhancement.

PubMed

Shokoohi, Hamid; S Boniface, Keith; M Abell, Bruce; Pourmand, Ali; Salimian, Mohammad

2016-01-01

Early detection of free air in the peritoneal cavity is vital in diagnosis of life-threatening emergencies, and can play a significant role in expediting treatment. We present a series of cases in which bedside ultrasound (US) in the emergency department accurately identified evidence of free intra-peritoneal air and echogenic (dirty) free fluid consistent with a surgical final diagnosis of a perforated hollow viscus. In all patients with suspected perforated viscus, clinicians were able to accurately identify the signs of pneumoperitoneum including enhanced peritoneal stripe sign (EPSS), peritoneal stripe reverberations, and focal air collections associated with dirty shadowing or distal multiple reflections as ring down artifacts. In all cases, hollow viscus perforation was confirmed surgically. It seems that, performing US in patients with suspected perforated viscus can accurately identify presence of intra-peritoneal echogenic or "dirty" free fluid as well as evidence of free air, and may expedite patient management.

Ultrasound assisted enhancement in natural dye extraction from beetroot for industrial applications and natural dyeing of leather.

PubMed

Sivakumar, Venkatasubramanian; Anna, J Lakshmi; Vijayeeswarri, J; Swaminathan, G

2009-08-01

There is a growing demand for eco-friendly/non-toxic colorants, specifically for health sensitive applications such as coloration of food and dyeing of child textile/leather garments. Recently, dyes derived from natural sources for these applications have emerged as an important alternative to potentially harmful synthetic dyes and pose need for suitable effective extraction methodologies. The present paper focus on the influence of process parameters for ultrasound assisted leaching of coloring matter from plant materials. In the present work, extraction of natural dye from beetroot using ultrasound has been studied and compared with static/magnetic stirring as a control process at 45 degrees C. The influence of process parameters on the extraction efficiency such as ultrasonic output power, time, pulse mode, effect of solvent system and amount of beetroot has been studied. The use of ultrasound is found to have significant improvement in the extraction efficiency of colorant obtained from beetroot. Based on the experiments it has been found that a mixture of 1:1 ethanol-water with 80W ultrasonic power for 3h contact time provided better yield and extraction efficiency. Pulse mode operation may be useful in reducing electrical energy consumption in the extraction process. The effect of the amount of beetroot used in relation to extraction efficiency has also been studied. Two-stage extraction has been studied and found to be beneficial for improving the yield for higher amounts of beetroot. Significant 8% enhancement in % yield of colorant has been achieved with ultrasound, 80W as compared to MS process both using 1:1 ethanol-water. The coloring ability of extracted beet dye has been tested on substrates such as leather and paper and found to be suitable for dyeing. Ultrasound is also found to be beneficial in natural dyeing of leather with improved rate of exhaustion. Both the dyed substrates have better color values for ultrasonic beet extract as inferred from

Effects of low-frequency ultrasound on heterogenous deacetylation of chitin.

PubMed

Ngo, Thi Hoai Duong; Ngo, Dang Nghia

2017-11-01

The effects of low frequency ultrasound to the heterogeneous deacetylation of chitin from the shell of white shrimp (Penaeus vannamei) were examined. The deacetylation process was carried out in the range of NaOH concentrations from 35% to 65% (w/w) with and without the ultrasound in the frequency of 37kHz, RMS=300W. The chitosan obtained was characterized in the degree of deacetylation, solubility, FT-IR and X-ray diffraction. The results showed that the behaviors of the deacetylation in two cases, with and without ultrasound, were similar but the ultrasound enhanced the deacetylation rate and therefore reduced the time of the reaction to get the same degree of deacetylation. The role of ultrasound in the process showed more clearly in the low concentration of sodium hydroxide, below 45% (w/w). At the higher concentration of sodium hydroxide, the influence of ultrasound on facilitating deacetylation decreased significantly, however, ultrasound was still keeping on its improving effect on the solubility of the chitosan obtained. The data from FT-IR and X-ray diffraction did not show any considerable change in structure of both kinds of chitosan. This study showed the potential of using low frequency ultrasound in enhancing the deacetylation of chitin for reducing the chemical consumption. Copyright © 2017 Elsevier B.V. All rights reserved.

Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

PubMed

Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

2016-02-01

Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P < .001). However, the thresholds for the two anesthetic methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. Thresholds for contrast-enhanced diagnostic US-induced injury of the microvasculature appear to be minimally affected by anesthetic methods. © 2016 by the American Institute of Ultrasound in Medicine.

An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study.

PubMed

Li, Yang; Ma, Jianguo; Martin, K Heath; Yu, Mingyue; Ma, Teng; Dayton, Paul A; Jiang, Xiaoning; Shung, K Kirk; Zhou, Qifa

2016-09-01

Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally. The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field-programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging. The system successfully obtained high-resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 μm diameter. For the first time, high-resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high-contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques.

Role of ultrasound in colorectal diseases.

PubMed

Bor, Renáta; Fábián, Anna; Szepes, Zoltán

2016-11-21

Ultrasound is an undervalued non-invasive examination in the diagnosis of colonic diseases. It has been replaced by the considerably more expensive magnetic resonance imaging and computed tomography, despite the fact that, as first examination, it can usefully supplement the diagnostic process. Transabdominal ultrasound can provide quick information about bowel status and help in the choice of adequate further examinations and treatment. Ultrasonography, as a screening imaging modality in asymptomatic patients can identify several colonic diseases such as diverticulosis, inflammatory bowel disease or cancer. In addition, it is widely available, cheap, non-invasive technique without the use of ionizing radiation, therefore it is safe to use in childhood or during pregnancy, and can be repeated at any time. New ultrasound techniques such as elastography, contrast enhanced and Doppler ultrasound, mini-probes rectal and transperineal ultrasonography have broadened the indication. It gives an overview of the methodology of various ultrasound examinations, presents the morphology of normal bowel wall and the typical changes in different colonic diseases. We will pay particular attention to rectal and transperineal ultrasound because of their outstanding significance in the diagnosis of rectal and perineal disorders. This article seeks to overview the diagnostic impact and correct indications of bowel ultrasound.

Laser Sources for Generation of Ultrasound

NASA Technical Reports Server (NTRS)

Wagner, James W.

1996-01-01

Two laser systems have been built and used to demonstrate enhancements beyond current technology used for laser-based generation and detection of ultrasound. The first system consisted of ten Nd:YAG laser cavities coupled electronically and optically to permit sequential bursts of up to ten laser pulses directed either at a single point or configured into a phased array of sources. Significant enhancements in overall signal-to-noise ratio for laser ultrasound incorporating this new source system was demonstrated, using it first as a source of narrowband ultrasound and secondly as a phased array source producing large enhanced signal displacements. A second laser system was implemented using ultra fast optical pulses from a Ti:Sapphire laser to study a new method for making laser generated ultrasonic measurements of thin films with thicknesses on the order of hundreds of angstroms. Work by prior investigators showed that such measurements could be made based upon fluctuations in the reflectivity of thin films when they are stressed by an arriving elastic pulse. Research performed using equipment purchased under this program showed that a pulsed interferometric system could be used as well as a piezoreflective detection system to measure pulse arrivals even in thin films with very low piezoreflective coefficients.

Markedly Enhanced Skeletal Muscle Transfection Achieved by the Ultrasound-Targeted Delivery of Non-Viral Gene Nanocarriers with Microbubbles

PubMed Central

Burke, Caitlin W.; Suk, Jung Soo; Kim, Anthony J.; Hsiang, Yu-Han J.; Klibanov, Alexander L.; Hanes, Justin; Price, Richard J.

2012-01-01

Our goal was to enhance ultrasound (US)-targeted skeletal muscle transfection through the use of poly(ethyleneglycol) (PEG)/polyethylenimine (PEI) nanocomplex gene carriers and adjustments to US and microbubble (MB) parameters. C57BL/6 mice received an intravenous infusion of MBs and either “naked” luciferase plasmid or luciferase plasmid condensed in PEG/PEI nanocomplexes. Pulsed ultrasound (1MHz; 0.6 MPa or 0.8 MPa) was applied to the right hindlimb for 12 mins. Luciferase activity in both hindlimbs was assessed at 3, 5, 7, and 10 days post-treatment by bioluminescent imaging. When targeted to hindlimb using unsorted MBs and 0.6 MPa US, 7 days after treatment, we observed a >60-fold increase in luciferase activity in PEG/PEI nanocomplex treated muscles over muscles treated with “naked” plasmid DNA. Luciferase activity was consistently greater after treatment with PEG/PEI nanocomplexes at 0.6 MPa as compared to 0.8 MPa. The combination of small diameter MBs and 0.6 MPa US also resulted in significantly greater gene expression when compared to concentration matched intramuscular injections, a control condition in which considerably more PEG/PEI nanocomplexes were present in tissue. This result suggests that, in addition to facilitating PEG/PEI nanocomplex delivery from the bloodstream to tissue, US enhances transfection via one or more secondary mechanisms, including increased cellular uptake and/or trafficking to the nucleus of PEG/PEI nanocomplexes. We conclude that PEG/PEI nanocomplexes may be used to markedly enhance the amplitude of US-MB-targeted skeletal muscle transfection and that activating “small” MBs with a moderate level (0.6 MPa) of acoustic pressure can further enhance these effects. PMID:22800583

Droplets, Bubbles and Ultrasound Interactions.

PubMed

Shpak, Oleksandr; Verweij, Martin; de Jong, Nico; Versluis, Michel

2016-01-01

The interaction of droplets and bubbles with ultrasound has been studied extensively in the last 25 years. Microbubbles are broadly used in diagnostic and therapeutic medical applications, for instance, as ultrasound contrast agents. They have a similar size as red blood cells, and thus are able to circulate within blood vessels. Perfluorocarbon liquid droplets can be a potential new generation of microbubble agents as ultrasound can trigger their conversion into gas bubbles. Prior to activation, they are at least five times smaller in diameter than the resulting bubbles. Together with the violent nature of the phase-transition, the droplets can be used for local drug delivery, embolotherapy, HIFU enhancement and tumor imaging. Here we explain the basics of bubble dynamics, described by the Rayleigh-Plesset equation, bubble resonance frequency, damping and quality factor. We show the elegant calculation of the above characteristics for the case of small amplitude oscillations by linearizing the equations. The effect and importance of a bubble coating and effective surface tension are also discussed. We give the main characteristics of the power spectrum of bubble oscillations. Preceding bubble dynamics, ultrasound propagation is introduced. We explain the speed of sound, nonlinearity and attenuation terms. We examine bubble ultrasound scattering and how it depends on the wave-shape of the incident wave. Finally, we introduce droplet interaction with ultrasound. We elucidate the ultrasound-focusing concept within a droplets sphere, droplet shaking due to media compressibility and droplet phase-conversion dynamics.

Multiparametric ultrasound in the detection of prostate cancer: a systematic review.

PubMed

Postema, Arnoud; Mischi, Massimo; de la Rosette, Jean; Wijkstra, Hessel

2015-11-01

To investigate the advances and clinical results of the different ultrasound modalities and the progress in combining them into multiparametric UltraSound (mpUS). A systematic literature search on mpUS and the different ultrasound modalities included: greyscale ultrasound, computerized transrectal ultrasound, Doppler and power Doppler techniques, dynamic contrast-enhanced ultrasound and (shear wave) elastography. Limited research available on combining ultrasound modalities has presented improvement in diagnostic performance. The data of two studies suggest that even adding a lower performing ultrasound modality to a better performing modality using crude methods can already improve the sensitivity by 13-51 %. The different modalities detect different tumours. No study has tried to combine ultrasound modalities employing a system similar to the PIRADS system used for mpMRI or more advanced classifying algorithms. Available evidence confirms that combining different ultrasound modalities significantly improves diagnostic performance.

Contrast-Enhanced Ultrasound Guided Biopsy of Undetermined Abdominal Lesions: A Multidisciplinary Decision-Making Approach.

PubMed

Mao, Feng; Dong, Yi; Ji, Zhengbiao; Cao, Jiaying; Wang, Wen-Ping

2017-01-01

Aim. To investigate the value of contrast-enhanced ultrasound (CEUS) guided biopsy of undetermined abdominal lesions in multidisciplinary treatment (MDT) decision-making approach. Methods. Between Jan 2012 and Dec 2015, 60 consecutive patients (male, 37; female, 23; mean age, 51.3 years ± 14.6) who presented with undetermined abdominal lesions were included. CEUS and core needle percutaneous biopsy was performed under real-time CEUS guidance in all lesions. Data were recorded and compared with conventional ultrasound (US) guidance group ( n = 75). All CEUS findings and clinical data were evaluated in MDT. Results. CEUS enabled the delimitation of more (88.3% versus 41.3%) and larger (14.1 ± 10.7 mm versus 32.3 ± 18.5 mm) nonenhanced necrotic areas. More inner (20.0% versus 6.7%) and surrounding (18.3% versus 2.7%) major vessels were visualized and avoided during biopsies. CEUS-guided biopsy increased the diagnostic accuracy from 93.3% to 98.3%, with correct diagnosis in 57 of 60 lesions (95.0%). The therapeutic plan was influenced by CEUS guided biopsies findings in the majority of patients (98.3%). Conclusion. The combination of CEUS guided biopsy and MDT decision-making approach is useful in the diagnostic work-up and therapeutic management.

Endogenous Catalytic Generation of O2 Bubbles for In Situ Ultrasound-Guided High Intensity Focused Ultrasound Ablation.

PubMed

Liu, Tianzhi; Zhang, Nan; Wang, Zhigang; Wu, Meiying; Chen, Yu; Ma, Ming; Chen, Hangrong; Shi, Jianlin

2017-09-26

High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor (catalase@MONs, abbreviated as C@M) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward H 2 O 2 , facilitating the continuous O 2 gas generation in a relatively mild manner even if incubated with 10 μM H 2 O 2 , which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The C@M nanoparticles could be accumulated within the H 2 O 2 -enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.

Intraprocedure contrast enhanced ultrasound: the value in assessing the effect of ultrasound-guided high intensity focused ultrasound ablation for uterine fibroids.

PubMed

Peng, Song; Hu, Liang; Chen, Wenzhi; Chen, Jinyun; Yang, Caiyong; Wang, Xi; Zhang, Rong; Wang, Zhibiao; Zhang, Lian

2015-04-01

To investigate the value of microbubble contrast-enhanced ultrasound (CEUS) in evaluating the treatment response of uterine fibroids to HIFU ablation. Sixty-eight patients with a solitary uterine fibroid from the First Affiliated Hospital of Chongqing Medical University were included and analyzed. All patients underwent pre- and post-treatment magnetic resonance imaging (MRI) with a standardized protocol, as well as pre-evaluation, intraprocedure, and immediate post-treatment CEUS. CEUS and MRI were compared by different radiologists. In comparison with MRI, CEUS showed that the size of fibroids, volume of fibroids, size of non-perfused regions, non-perfused volume (NPV) or fractional ablation (NPV ratio) was similar to that of MRI. In terms of CEUS examination results, the median volume of fibroids was 75.2 (interquartile range, 34.2-127.3) cm(3), the median non-perfused volume was 54.9 (interquartile range, 28.0-98.1) cm(3), the mean fractional ablation was 83.7±13.6 (range, 30.0-100.0)%. In terms of MRI examination results, the median volume of fibroids was 74.1 (interquartile range, 33.4-116.2) cm(3). On the basis of contrast-enhanced T1-weighted images immediately after HIFU treatment, the median non-perfused volume was 58.5 (interquartile range, 27.7-100.0) cm(3), the average fractional ablation was 84.2±14.2 (range, 40.0-100.0)%. CEUS clearly showed the size of fibroids and the non-perfused areas of the fibroid. Results from CEUS correlated well with results obtained from MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

Impedance-controlled ultrasound probe

NASA Astrophysics Data System (ADS)

Gilbertson, Matthew W.; Anthony, Brian W.

2011-03-01

An actuated hand-held impedance-controlled ultrasound probe has been developed. The controller maintains a prescribed contact state (force and velocity) between the probe and a patient's body. The device will enhance the diagnostic capability of free-hand elastography and swept-force compound imaging, and also make it easier for a technician to acquire repeatable (i.e. directly comparable) images over time. The mechanical system consists of an ultrasound probe, ball-screw-driven linear actuator, and a force/torque sensor. The feedback controller commands the motor to rotate the ball-screw to translate the ultrasound probe in order to maintain a desired contact force. It was found that users of the device, with the control system engaged, maintain a constant contact force with 15 times less variation than without the controller engaged. The system was used to determine the elastic properties of soft tissue.

High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography.

PubMed

Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath; Ozgun, Kathryn A; Rojas, Juan D; Foster, F Stuart; Dayton, Paul A

2017-04-01

Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.

Frequency-dependent ultrasound-induced transformation in E. coli.

PubMed

Deeks, Jeremy; Windmill, James; Agbeze-Onuma, Maduka; Kalin, Robert M; Argondizza, Peter; Knapp, Charles W

2014-12-01

Ultrasound-enhanced gene transfer (UEGT) is continuing to gain interest across many disciplines; however, very few studies investigate UEGT efficiency across a range of frequencies. Using a variable frequency generator, UEGT was tested in E. coli at six ultrasonic frequencies. Results indicate frequency can significantly influence UEGT efficiency positively and negatively. A frequency of 61 kHz improved UEGT efficiency by ~70 % higher, but 99 kHz impeded UEGT to an extent worse than no ultrasound exposure. The other four frequencies (26, 133, 174, and 190 kHz) enhanced transformation compared to no ultrasound, but efficiencies did not vary. The influence of frequency on UEGT efficiency was observed across a range of operating frequencies. It is plausible that frequency-dependent dynamics of mechanical and chemical energies released during cavitational-bubble collapse (CBC) are responsible for observed UEGT efficiencies.

Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS.

PubMed

Schellhaas, Barbara; Görtz, Ruediger S; Pfeifer, Lukas; Kielisch, Christian; Neurath, Markus F; Strobel, Deike

2017-09-01

A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; p<0.01). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value for ESCULAP/CEUS-LI-RADS were 94.3%/72.4%; 61.5%/69.2%; 94.3%/94%; and 61.5%/27.3%, respectively.The diagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the

Contrast-Enhanced Ultrasound Improves the Pathological Outcomes of US-Guided Core Needle Biopsy That Targets the Viable Area of Anterior Mediastinal Masses

PubMed Central

Zhou, Jian-hua; Shan, Hong-bo; Ou, Wei; Mo, Yun-xian; Xiang, Jin; Wang, Yu; Wang, Si-yu

2018-01-01

Based on the option that ultrasound-guided core needle biopsy (US-CNB) of the enhanced portion of anterior mediastinal masses (AMMs) identified by contrast-enhanced ultrasound (CEUS) would harvest viable tissue and benefit the histological diagnoses, a retrospective study was performed to elucidate the correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found that CEUS potentially improved the diagnostic yield of AMMs compared with conventional US with a significant increase in the cellularity of samples. Furthermore, the marginal blood flow signals and absence of necrosis can predict the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of AMMs, as verified by CEUS, was able to harvest sufficient tissue with more cellularity that could be used for ancillary studies and improve the diagnostic yield. And CEUS was recommended to those patients with AMMs undergoing repeated US-CNB, with the absence of marginal blood signals or presence of necrosis. PMID:29581992

Ultrasound pregnancy

MedlinePlus

Pregnancy sonogram; Obstetric ultrasonography; Obstetric sonogram; Ultrasound - pregnancy; IUGR - ultrasound; Intrauterine growth - ultrasound; Polyhydramnios - ultrasound; Oligohydramnios - ultrasound; Placenta previa - ultrasound; Multiple pregnancy - ultrasound; ...

Longitudinal Ultrasound Education Track Curriculum Implemented Within an Emergency Medicine Residency Program.

PubMed

Boulger, Creagh; Adams, Daniel Z; Hughes, Daralee; Bahner, David P; King, Andrew

2017-06-01

Emergency Medicine residency programs offer ultrasound-focused curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. Although some programs offer advanced clinical tracks in ultrasound, no standard curriculum exists. We sought to establish a well-defined ultrasound track curriculum to allow interested residents to develop advanced clinical skills and scholarship within this academic niche. The curriculum involves a greater number of clinical scans, ultrasound-focused scholarly and quality improvement projects, enhanced faculty-driven ultrasound focused didactics, and participation at a national ultrasound conference to receive certification. Successful ultrasound scholarly tracks can provide residents with the potential to obtain fellowships or competency beyond ACGME requirements. © 2017 by the American Institute of Ultrasound in Medicine.

Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy

NASA Astrophysics Data System (ADS)

Crake, Calum; Meral, F. Can; Burgess, Mark T.; Papademetriou, Iason T.; McDannold, Nathan J.; Porter, Tyrone M.

2017-08-01

Focused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure. Here, we employed phase-shift nanoemulsions (PSNE) embedded in tissue phantoms to promote cavitation and hence temperature rise induced by FUS. In addition, we incorporated passive acoustic mapping (PAM) alongside simultaneous MR thermometry in order to visualize both acoustic emissions and temperature rise, within the bore of a full scale clinical MRI scanner. Focal cavitation of PSNE could be resolved using PAM and resulted in accelerated heating and increased the maximum elevated temperature measured via MR thermometry compared to experiments without nanoemulsions. Over time, the simultaneously acquired acoustic and temperature maps show translation of the focus of activity towards the FUS transducer, and the magnitude of the increase in cavitation and focal shift both increased with nanoemulsion concentration. PAM results were well correlated with MRI thermometry and demonstrated greater sensitivity, with the ability to detect cavitation before enhanced heating was observed. The results suggest that PSNE could be beneficial for enhancement of thermal focused ultrasound therapies and that PAM could be a critical tool for monitoring this process.

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging

NASA Astrophysics Data System (ADS)

Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

2016-09-01

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

PubMed

Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

2016-09-15

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

PubMed

Fekri, Farnaz; Delos Santos, Ralph Christian; Karshafian, Raffi; Antonescu, Costin N

2016-01-01

Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME) for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR), and distinct mechanism(s) that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may improve targeted

[Polymeric drug carriers activated by ultrasounds energy].

PubMed

Kik, Krzysztof; Lwow, Felicja; Szmigiero, Leszek

2007-01-01

In the last two decades an extensive research on the employment of ultrasounds in anticancer therapy has been noticed. So far ultrasounds have been widely used in medicine for diagnostic purposes (ultrasonography), but their great therapeutic potential and the development of polymer based antineoplastic drug carriers have persuaded many investigators to start research on the employment of ultrasounds in anticancer therapy. A new therapeutic concept based on the controlled drug's molecules release from their transporting polymer carriers has been proposed. Cavitation, a phenomenon characteristic for the action of ultrasounds, is used to destroy polymeric drug carriers and for drug release in target sites. The sonodynamic therapy (SDT) which utilizes ultrasonic waves for "acoustic drug activation" leading to the enhancement of cytotoxic activity of some drugs has also been developed. Furthermore, a long standing research on ultrasounds resulted in a new concept based on hyperthermia. This method of cancer treatment does not require any chemotherapeutic agent to be applied.

Common-path conoscopic interferometry for enhanced picosecond ultrasound detection

NASA Astrophysics Data System (ADS)

Liu, Liwang; Guillet, Yannick; Audoin, Bertrand

2018-05-01

We report on a common-path implementation of conoscopic interferometry in picosecond pump-probe reflectometry for simple and efficient detection of picosecond ultrasounds. The interferometric configuration proposed here is greatly simplified, involving only the insertion of a birefringent crystal in a standard reflectometry setup. Our approach is demonstrated by the optical detection of coherent acoustic phonons propagating through thin metal films under two representative geometries, one a particular case where the crystal slab is part of a sample as substrate of a metal film, and the other a more general case where the crystal slab is independent of the sample as part of the detection system. We first illustrate the former with a 300 nm thin film of polycrystalline titanium, deposited by physical vapor deposition on top of a 1 mm-thick uniaxial (0001) sapphire crystal. A signal-to-noise ratio (SNR) enhancement of more than 15 dB is achieved compared to conventional reflectometry. Next, the general case is demonstrated with a 900 nm-tungsten film sputtered on a silicon wafer substrate. More echoes can be discriminated by using the reported approach compared to standard reflectometry, which confirms the improvement in SNR and suggests broad applications for the reported method.

Ultrasound-guided drug delivery in cancer

PubMed Central

2017-01-01

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy. PMID:28607323

Transvaginal ultrasound

MedlinePlus

Endovaginal ultrasound; Ultrasound - transvaginal; Fibroids - transvaginal ultrasound; Vaginal bleeding - transvaginal ultrasound; Uterine bleeding - transvaginal ultrasound; Menstrual bleeding - transvaginal ultrasound; ...

Successful strategies for integrating bedside ultrasound into undergraduate medical education.

PubMed

Palma, James K

2015-04-01

Nearly all physician specialties currently utilize bedside ultrasound, and its applications continue to expand. Bedside ultrasound is becoming a core skill for physicians; as such, it should be taught during undergraduate medical education. When ultrasound is integrated in a longitudinal manner beginning in the preclerkship phase of medical school, it not only enhances teaching the basic science topics of anatomy, physiology, and pathology but also ties those skills and knowledge to the clerkship phase and medical decision-making. Bedside ultrasound is a natural bridge from basic science to clinical science. The Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine is currently in its fourth year of implementing an integrated ultrasound curriculum in the school of medicine. In our experience, successful integration of a bedside ultrasound curriculum should: align with unique focuses of a medical schools' mission, simplify complex anatomy through multimodal teaching, correlate to teaching of the physical examination, solidify understanding of physiology and pathology, directly link to other concurrent content, narrow differential diagnoses, enhance medical decision-making, improve procedural skills, match to year-group skillsets, develop teaching and leadership abilities, and have elective experiences for advanced topics. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.

PubMed

Shoji, Sunao; Tonooka, Akiko; Hashimoto, Akio; Nakamoto, Masahiko; Tomonaga, Tetsuro; Nakano, Mayura; Sato, Haruhiro; Terachi, Toshiro; Koike, Junki; Uchida, Toyoaki

2014-09-01

Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer. © 2014 The Japanese Urological Association.

Theranostic Oxygen Delivery Using Ultrasound and Microbubbles

PubMed Central

Kwan, James J.; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Means to overcome tumor hypoxia have been the subject of clinical investigations since the 1960's; however these studies have yet to find a treatment which is widely accepted. It has been known for nearly a century that hypoxic cells are more resistant to radiotherapy than aerobic cells, and tumor hypoxia is a major factor leading to the resistance of tumors to radiation treatment as well as several cytotoxic agents. In this manuscript, the application of ultrasound combined with oxygen-carrier microbubbles is demonstrated as a method to locally increase dissolved oxygen. Microbubbles can also be imaged by ultrasound, thus providing the opportunity for image-guided oxygen delivery. Simulations of gas diffusion and microbubble gas exchange show that small amounts (down to 5 vol%) of a low-solubility osmotic gas can substantially increase microbubble persistence and therefore production rates and stability of oxygen-carrier microbubbles. Simulations also indicate that the lipid shell can be engineered with long-chain lipids to increase oxygen payload during in vivo transit. Experimental results demonstrate that the application of ultrasound to destroy the microbubbles significantly enhances the local oxygen release. We propose this technology as an application for ultrasound image-guided release of oxygen directly to hypoxic tissue, such as tumor sites to enhance radiotherapy. PMID:23382774

Contrast-enhanced ultrasound and computed tomography findings of granulomatosis with polyangiitis presenting with multiple intrarenal microaneurysms: A case report.

PubMed

Kim, Youe Ree; Lee, Young Hwan; Lee, Jong-Ho; Yoon, Kwon-Ha

Granulomatosis with polyangiitis (GPA) is a systemic disorder that affects small- and medium- sized vessels in many organs. Although the kidneys are the second most commonly involved organ in patients with GPA, its manifestation as multiple intrarenal aneurysms is rare. We report an unusual manifestation of GPA with multiple intrarenal microaneurysms, as demonstrated by contrast-enhanced ultrasound and computed tomography. Copyright © 2017 Elsevier Inc. All rights reserved.

Endoscopic ultrasound: state-of-the-art GI tumor staging

NASA Astrophysics Data System (ADS)

Trowers, Eugene A.

1999-06-01

Videoendoscopy has truly enlarged the scope of diagnostic and therapeutic gastroenterology. However, videoendoscopic examinations are limited to the mucosal surface. Endoscopic ultrasound allows the endoscopist a view beyond the intestinal wall which opens the door to a variety of new gastroenterologic techniques. The evaluation of plain images in combination with contrast-enhanced imags has been found to be helpful when applied to CT and MRI. A similar advantage may be found for endoscopic ultrasound (EUS) studies. The efficacy of EUS with and without contrast enhancement is critically reviewed.

Effects of ultrasound and ultrasound contrast agent on vascular tissue

PubMed Central

2012-01-01

Background Ultrasound (US) imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology. Aim While ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail. Methods and results In the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) staining of treated aortas demonstrated incipient apoptosis in the endothelium. Conclusions Taken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question. PMID:22805356

Ultrasound

MedlinePlus

... community Home > Pregnancy > Prenatal care > Ultrasound during pregnancy Ultrasound during pregnancy E-mail to a friend Please ... you. What are some reasons for having an ultrasound? Your provider uses ultrasound to do several things, ...

Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients.

PubMed

Schellhaas, Barbara; Pfeifer, Lukas; Kielisch, Christian; Goertz, Ruediger Stephan; Neurath, Markus F; Strobel, Deike

2018-06-07

 This pilot study aimed at assessing interobserver agreement with two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.  Focal liver lesions in 55 high-risk patients were assessed independently by three blinded observers with two standardized CEUS algorithms: ESCULAP (Erlanger Synopsis of Contrast-Enhanced Ultrasound for Liver Lesion Assessment in Patients at risk) and ACR-CEUS-LI-RADSv.2016 (American College of Radiology CEUS-Liver Imaging Reporting and Data System). Lesions were categorized according to size and ultrasound contrast enhancement in the arterial, portal-venous and late phase. Interobserver agreement for assessment of enhancement pattern and categorization was compared between both CEUS algorithms. Additionally, diagnostic accuracy for the definitive diagnosis of HCC was compared. Histology and/or CE-MRI and follow-up served as reference standards.  55 patients were included in the study (male/female, 44/ 11; mean age: 65.9 years). 90.9 % had cirrhosis. Histological findings were available in 39/55 lesions (70.9 %). Reference standard of the 55 lesions revealed 48 HCCs, 2 intrahepatic cholangiocellular carcinomas (ICCs), and 5 non-HCC-non-ICC lesions. Interobserver agreement was moderate to substantial for arterial phase hyperenhancement (ĸ = 0.53 - 0.67), and fair to moderate for contrast washout in the portal-venous or late phase (ĸ = 0.33 - 0.53). Concerning the CEUS-based algorithms, the interreader agreement was substantial for the ESCULAP category (ĸ = 0.64 - 0.68) and fair for the CEUS-LI-RADS ® category (ĸ = 0.3 - 0.39). Disagreement between observers was mostly due to different perception of washout.  Interobserver agreement is better for ESCULAP than for CEUS-LI-RADS ® . This is mostly due to the fact that perception of contrast washout varies between different observers. However, interobserver agreement is good for

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

PubMed

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

Applications of ultrasound to chiral crystallization, resolution and deracemization.

PubMed

Xiouras, Christos; Fytopoulos, Antonios; Jordens, Jeroen; Boudouvis, Andreas G; Van Gerven, Tom; Stefanidis, Georgios D

2018-05-01

Industrial synthesis of enantiopure compounds is nowadays heavily based on the separation of racemates through crystallization processes. Although the application of ultrasound in solution crystallization processes (sonocrystallization) has become a promising emerging technology, offering several benefits (e.g. reduction of the induction time and narrowing of the metastable zone width, control over the product size, shape and polymorphic modification), little attention has been paid so far to the effects of ultrasound on chiral crystallization processes. Several recent studies have reported on the application of acoustic energy to crystallization processes that separate enantiomers, ranging from classical (diastereomeric) resolution and preferential crystallization to new and emerging processes such as attrition-enhanced deracemization (Viedma ripening). A variety of interesting effects have been observed, which include among others, enhanced crystallization yield with higher enantiomeric purity crystals, spontaneous mirror symmetry breaking crystallization, formation of metastable conglomerate crystals and enhanced deracemization rates. The objective of this review is to provide an overview of the effects of ultrasound on chiral crystallization and outline several aspects of interest in this emerging field. Copyright © 2018 Elsevier B.V. All rights reserved.

Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

PubMed

Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

2011-10-01

The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

PubMed Central

Jang, Jae Young; Kim, Moon Young; Jeong, Soung Won; Kim, Tae Yeob; Kim, Seung Up; Lee, Sae Hwan; Suk, Ki Tae; Park, Soo Young; Woo, Hyun Young; Kim, Sang Gyune; Heo, Jeong; Baik, Soon Koo; Kim, Hong Soo

2013-01-01

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data. PMID:23593604

Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

NASA Astrophysics Data System (ADS)

Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

2016-09-01

It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review.

PubMed

Vinke, Elisabeth J; Kortenbout, Anna J; Eyding, Jens; Slump, Cornelis H; van der Hoeven, Johannes G; de Korte, Chris L; Hoedemaekers, Cornelia W E

2017-12-01

Contrast-enhanced ultrasound (CEUS) has been suggested as a new method to measure cerebral perfusion in patients with acute brain injury. In this systematic review, the tolerability, repeatability, reproducibility and accuracy of different CEUS techniques for the quantification of cerebral perfusion were assessed. We selected studies published between January 1994 and March 2017 using CEUS to measure cerebral perfusion. We included 43 studies (bolus kinetics n = 31, refill kinetics n = 6, depletion kinetics n = 6) with a total of 861 patients. Tolerability was reported in 28 studies describing 12 patients with mild and transient side effects. Repeatability was assessed in 3 studies, reproducibility in 2 studies and accuracy in 19 studies. Repeatability was high for experienced sonographers and significantly lower for less experienced sonographers. Reproducibility of CEUS was not clear. The sensitivity and specificity of CEUS for the detection of cerebral ischemia ranged from 75% to 96% and from 60% to 100%. Limited data on repeatability, reproducibility and accuracy may suggest that this technique could be feasible for use in acute brain injury patients. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Standards of ultrasound imaging of the adrenal glands

PubMed Central

Jakubowski, Wiesław S.; Dobruch-Sobczak, Katarzyna; Kasperlik-Załuska, Anna A.

2015-01-01

Adrenal glands are paired endocrine glands located over the upper renal poles. Adrenal pathologies have various clinical presentations. They can coexist with the hyperfunction of individual cortical zones or the medulla, insufficiency of the adrenal cortex or retained normal hormonal function. The most common adrenal masses are tumors incidentally detected in imaging examinations (ultrasound, tomography, magnetic resonance imaging), referred to as incidentalomas. They include a range of histopathological entities but cortical adenomas without hormonal hyperfunction are the most common. Each abdominal ultrasound scan of a child or adult should include the assessment of the suprarenal areas. If a previously non-reported, incidental solid focal lesion exceeding 1 cm (incidentaloma) is detected in the suprarenal area, computed tomography or magnetic resonance imaging should be conducted to confirm its presence and for differentiation and the tumor functional status should be determined. Ultrasound imaging is also used to monitor adrenal incidentaloma that is not eligible for a surgery. The paper presents recommendations concerning the performance and assessment of ultrasound examinations of the adrenal glands and their pathological lesions. The article includes new ultrasound techniques, such as tissue harmonic imaging, spatial compound imaging, three-dimensional ultrasound, elastography, contrast-enhanced ultrasound and parametric imaging. The guidelines presented above are consistent with the recommendations of the Polish Ultrasound Society. PMID:26807295

Using low-frequency ultrasound to improve the optical clearing of porcine skin

NASA Astrophysics Data System (ADS)

Zhong, Huiqing; Guo, Zhouyi; Wei, Huajiang; Zhang, Zude; Zeng, Changchun; Zhai, Juan; He, Yonghong

2008-12-01

The glycerol used as an enhancer for tissue optical clearing technique has been researched. However, using it and a physical way of ultrasound enhance optical clearing of tissue reported a few. We researched that the ultrasound whether can improve the optical clearing of dealt with 80% glycerol tissue. The fresh porcine skins divided into four groups. The first group was not dealt with by ultrasound and 80% glycerol, the second group was dealt with by only ultrasound, the third group was dealt with by 80% glycerol and no by ultrasound, and the fourth group was dealt with by both 80% glycerol and ultrasound. And we measured changes in optical scattering of the porcine skins under treatment with OCT. From the OCT images show that the fourth group changed very faster than the other's during the 0~15 min. And it can be clearly seen that there is a significant improvement in the light penetration depth and imaging contrast in a shorter time. It is possible that the low-frequency ultrasound can make disordering of the stratum corneum lipids of the porcine skin (because the cavitation has happened), and improve the speed of 80% glycerol through the stratum corneum of skin. These results proved that using 80% glycerol with the ultrasound can better improve the optical clearing of tissue.

Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

2016-04-01

Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

Contrast-enhanced ultrasound may distinguish gallbladder adenoma from cholesterol polyps: a prospective case-control study.

PubMed

Fei, Xiang; Lu, Wen-Ping; Luo, Yu-Kun; Xu, Jian-Hon; Li, Yan-Mi; Shi, Huai-Yin; Jiao, Zi-Yu; Li, Hong-tian

2015-10-01

The aim of this study was to find the independent risk factors related with gallbladder (GB) adenoma compared to cholesterol polyp by contrast-enhanced ultrasound (CEUS). Between January 2010 and September 2014, a total of 122 consecutive patients undergoing cholecystectomy for GB polypoid lesions were enrolled. Before cholecystectomy, each patient underwent conventional US and CEUS examination and all image features were documented. The patients were divided into adenoma group and cholesterol polyp group according to the pathological findings. All the image features between two groups were statistically compared. There were differences in patient age, lesion size, echogenicity, and vascularity of lesion between two groups (P < 0.05). There were differences in stalk width and enhancement intensity between the two groups (P < 0.05). Multiple logistic regression analysis proved that enhancement intensity, stalk of lesion, and vascularity were the independent risk factors related with GB adenoma (P < 0.05). CEUS could offer useful information to distinguish adenoma from cholesterol polyp. The treatment algorithm for gallbladder polyp lesions would likely benefit from CEUS as a routine imaging investigation, especially in cases where the polyp is larger than 1 cm.

Pulsed-High Intensity Focused Ultrasound (HIFU) Exposures for Enhanced Delivery of Therapeutics: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Frenkel, Victor; Deng, Cheri; O'Neill, Brian E.; Quijano, Jade; Stone, Michael J.; Dromi, Sergio; Hunter, Finie; Xie, Jianwu; Quinn, Timothy P.; Wood, Bradford J.; Li, King C. P.

2006-05-01

The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed.

Volume quantification by contrast-enhanced ultrasound: an in-vitro comparison with true volumes and thermodilution.

PubMed

Herold, Ingeborg H F; Russo, Gianna; Mischi, Massimo; Houthuizen, Patrick; Saidov, Tamerlan; van het Veer, Marcel; van Assen, Hans C; Korsten, Hendrikus H M

2013-10-17

Contrast-enhanced ultrasound (CEUS) has recently been proposed as a minimally- invasive, alternative method for blood volume measurement. This study aims at comparing the accuracy of CEUS and the classical thermodilution techniques for volume assessment in an in-vitro set-up. The in-vitro set-up consisted of a variable network between an inflow and outflow tube and a roller pump. The inflow and outflow tubes were insonified with an ultrasound array transducer and a thermistor was placed in each tube. Indicator dilution curves were made by injecting indicator which consisted of an ultrasound-contrast-agent diluted in ice-cold saline. Both acoustic intensity- and thermo-dilution curves were used to calculate the indicator mean transit time between the inflow and outflow tube. The volumes were derived by multiplying the estimated mean transit time by the flow rate. We compared the volumes measured by CEUS with the true volumes of the variable network and those measured by thermodilution by Bland-Altman and intraclass-correlation analysis. The measurements by CEUS and thermodilution showed a very strong correlation (rs = 0.94) with a modest volume underestimation by CEUS of -40 ± 28 mL and an overestimation of 84 ± 62 mL by thermodilution compared with the true volumes. Both CEUS and thermodilution showed a high statistically significant correlation with the true volume (rs = 0.97 (95% CI, 0.95 - 0.98; P<0.0001) and rs = 0.96 (95% CI, 0.94 - 0.98; P<0.0001, respectively). CEUS volume estimation provides a strong correlation with both the true volumes in-vitro and volume estimation by thermodilution. It may therefore represent an interesting alternative to the standard, invasive thermodilution technique.

Transvaginal Ultrasound for the Diagnosis of Abnormal Uterine Bleeding.

PubMed

Wheeler, Karen C; Goldstein, Steven R

2017-03-01

Transvaginal ultrasound is the first-line imaging test for the evaluation of abnormal uterine bleeding in both premenopausal and postmenopausal women. Transvaginal ultrasound can be used to diagnose structural causes of abnormal bleeding such as polyps, adenomyosis, leiomyomas, hyperplasia, and malignancy, and can also be beneficial in making the diagnosis of ovulatory dysfunction. Traditional 2-dimensional imaging is often enhanced by the addition of 3-dimension imaging with coronal reconstruction and saline infusion sonohysterography. In this article we discuss specific ultrasound findings and technical considerations useful in the diagnosis of abnormal uterine bleeding.

Duplex ultrasound

MedlinePlus

Vascular ultrasound; Peripheral vascular ultrasound ... A duplex ultrasound combines: Traditional ultrasound: This uses sound waves that bounce off blood vessels to create pictures. Doppler ultrasound: This ...

Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

PubMed

Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

2015-01-01

Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular imaging with targeted contrast ultrasound.

PubMed

Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

2009-01-01

Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

Application of Ultrasound Energy as a New Drug Delivery System

NASA Astrophysics Data System (ADS)

Tachibana, Katsuro; Tachibana, Shunro

1999-05-01

Ultrasound has been in use for the last three decades as amodality for diagnostic imaging in medicine. Recently, there have beennumerous reports on the application of nonthermal ultrasound energyfor targeting or controlling drug release. This new concept oftherapeutic ultrasound combined with drugs has led to much excitementin various medical fields. Ultrasound energy can enhance the effectsof thrombolytic agents such as urokinase. Therapeutic ultrasoundcatheters are currently being developed for treatment ofcardiovascular diseases. Devices with ultrasound transducers implantedin transdermal drug patches are also being evaluated for possibledelivery of insulin through the skin. Chemical activation of drugs byultrasound energy for treatment of cancers is another new fieldrecently termed “Sonodynamic Therapy”. Various examples of ultrasoundapplication are under investigation which could lead to revolutionarydrug delivery systems in the future.

Blotting from PhastGel to Membranes by Ultrasound.

PubMed

Kost, Joseph; Azagury, Aharon

2015-01-01

Ultrasound based approach for enhanced protein blotting is proposed. Three minutes of ultrasound exposure (1 MHz, 2.5 W/cm(2)) was sufficient for a clear transfer of proteins from a polyacrylamide gel (PhastGel) to nitrocellulose or Nylon 66 Biotrans membrane. The proteins evaluated were prestained sodium dodecyl sulfate-polyacrylamide standards (18,500-106,000 Da) and 14C-labeled Rainbow protein molecular weight markers (14,300-200,000 Da).

Blotting from PhastGel to membranes by ultrasound.

PubMed

Kost, Joseph

2009-01-01

Ultrasound-based approach for enhanced protein blotting is proposed. Three minutes of ultrasound exposure (1 MHz, 2.5 W/cm(2)) was sufficient for a clear transfer of proteins from a polyacrylamide gel (PhastGel) to nitrocellulose or Nylon 66 Biotrans membrane. The proteins evaluated were prestained sodium dodecyl sulfate-polyacrylamide standards (18,500-106,000 Da) and (14)C-labeled Rainbow protein molecular weight markers (14,300-200,000 Da).

Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application.

PubMed

Cancel, Limary M; Tarbell, John M; Ben-Jebria, Abdellaziz

2004-09-01

Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.

Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery.

PubMed

Ferrara, Katherine W; Borden, Mark A; Zhang, Hua

2009-07-21

Ultrasound pressure waves can map the location of lipid-stabilized gas micro-bubbles after their intravenous administration in the body, facilitating an estimate of vascular density and microvascular flow rate. Microbubbles are currently approved by the Food and Drug Administration as ultrasound contrast agents for visualizing opacification of the left ventricle in echocardiography. However, the interaction of ultrasound waves with intravenously-injected lipid-shelled particles, including both liposomes and microbubbles, is a far richer field. Particles can be designed for molecular imaging and loaded with drugs or genes; the mechanical and thermal properties of ultrasound can then effect localized drug release. In this Account, we provide an overview of the engineering of lipid-shelled microbubbles (typical diameter 1000-10 000 nm) and liposomes (typical diameter 65-120 nm) for ultrasound-based applications in molecular imaging and drug delivery. The chemistries of the shell and core can be optimized to enhance stability, circulation persistence, drug loading and release, targeting to and fusion with the cell membrane, and therapeutic biological effects. To assess the biodistribution and pharmacokinetics of these particles, we incorporated positron emission tomography (PET) radioisotopes on the shell. The radionuclide (18)F (half-life approximately 2 h) was covalently coupled to a dipalmitoyl lipid, followed by integration of the labeled lipid into the shell, facilitating short-term analysis of particle pharmacokinetics and metabolism of the lipid molecule. Alternately, labeling a formed particle with (64)Cu (half-life 12.7 h), after prior covalent incorporation of a copper-chelating moiety onto the lipid shell, permits pharmacokinetic study of particles over several days. Stability and persistence in circulation of both liposomes and microbubbles are enhanced by long acyl chains and a poly(ethylene glycol) coating. Vascular targeting has been demonstrated with

Photo-Acoustic Ultrasound Imaging to Distinguish Benign from Malignant Prostate Cancer

DTIC Science & Technology

2016-09-01

from the inside out. Ultrasound imaging provides a basic view of the structure of the prostate while photoacoustic contrast is predicted to enhance...University Page 2 of 13 1. INTRODUCTION: Ultrasound imaging uses sound waves at frequencies above the human hearing range to image organs within the body...An ultrasound transducer delivers a pulse of acoustic energy into the area of interest and listens for the echoes which return as the sound waves

High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology

PubMed Central

Malietzis, G; Monzon, L; Hand, J; Wasan, H; Leen, E; Abel, M; Muhammad, A; Abel, P

2013-01-01

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy. PMID:23403455

Enhanced Ultrasound Visualization of Bracytherapy Seeds by a Novel Magnetically Induced Motion Imaging Method

DTIC Science & Technology

2008-04-01

We report our progress in developing Magnetically Induced Motion Imaging (MIMI) for unambiguous identification and localization brachytherapy seeds ...in ultrasound images. Coupled finite element and ultrasound imaging simulations have been performed to demonstrate that seeds are detectable with MIMI

Automatic ultrasound image enhancement for 2D semi-automatic breast-lesion segmentation

NASA Astrophysics Data System (ADS)

Lu, Kongkuo; Hall, Christopher S.

2014-03-01

Breast cancer is the fastest growing cancer, accounting for 29%, of new cases in 2012, and second leading cause of cancer death among women in the United States and worldwide. Ultrasound (US) has been used as an indispensable tool for breast cancer detection/diagnosis and treatment. In computer-aided assistance, lesion segmentation is a preliminary but vital step, but the task is quite challenging in US images, due to imaging artifacts that complicate detection and measurement of the suspect lesions. The lesions usually present with poor boundary features and vary significantly in size, shape, and intensity distribution between cases. Automatic methods are highly application dependent while manual tracing methods are extremely time consuming and have a great deal of intra- and inter- observer variability. Semi-automatic approaches are designed to counterbalance the advantage and drawbacks of the automatic and manual methods. However, considerable user interaction might be necessary to ensure reasonable segmentation for a wide range of lesions. This work proposes an automatic enhancement approach to improve the boundary searching ability of the live wire method to reduce necessary user interaction while keeping the segmentation performance. Based on the results of segmentation of 50 2D breast lesions in US images, less user interaction is required to achieve desired accuracy, i.e. < 80%, when auto-enhancement is applied for live-wire segmentation.

Sonodynamic therapy--a review of the synergistic effects of drugs and ultrasound.

PubMed

Rosenthal, Ionel; Sostaric, Joe Z; Riesz, Peter

2004-09-01

Sonodynamic therapy, the ultrasound dependent enhancement of cytotoxic activities of certain compounds (sonosensitizers) in studies with cells in vitro and in tumor bearing animals, is reviewed. The attractive features of this modality for cancer treatment emerges from the ability to focus the ultrasound energy on malignancy sites buried deep in tissues and to locally activate a preloaded sonosensitizer. Possible mechanisms of sonodynamic therapy include generation of sonosensitizer derived radicals which initiate chain peroxidation of membrane lipids via peroxyl and/or alkoxyl radicals, the physical destabilization of the cell membrane by the sonosensitizer thereby rendering the cell more susceptible to shear forces or ultrasound enhanced drug transport across the cell membrane (sonoporation). Evidence against the role of singlet oxygen in sonodynamic therapy is discussed. The mechanism of sonodynamic therapy is probably not governed by a universal mechanism, but may be influenced by multiple factors including the nature of the biological model, the sonosensitizer and the ultrasound parameters. The current review emphasizes the effect of ultrasound induced free radicals in sonodynamic therapy.

Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

PubMed

Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

2016-01-01

Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier.

Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

PubMed

Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

2017-05-01

The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P < .001; Responder group: 10.54 seconds; nonresponder group: 15.33 seconds). The2 groups had opposite changes in RT (continuous increase in the responder group and transient reduction in the nonresponder). The RT of metastatic foci was normalized to that of adjacent normal liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

Combined Ultrasound and MR Imaging to Guide Focused Ultrasound Therapies in the Brain

PubMed Central

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-01-01

Purpose Several emerging therapies with potential for use in the brain harness effects produced by acoustic cavitation – the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength, and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. Materials and Methods We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. Results The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. Conclusion While preliminary, these data clearly demonstrate, for the first time, that is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate it will also prove to

Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain

NASA Astrophysics Data System (ADS)

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-07-01

Several emerging therapies with potential for use in the brain, harness effects produced by acoustic cavitation—the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. While preliminary, these data clearly demonstrate, for the first time, that it is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate that it will also prove to be an important research tool that will

Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots

PubMed Central

Chernysh, Irina N.; Everbach, E. Carr; Purohit, Prashant K.; Weisel, John W.

2016-01-01

Summary Background Ultrasound accelerates tissue-type plasminogen activator (t-PA)-induced fibrinolysis of clots in vitro and in vivo. Objective To identify mechanisms for the enhancement of t-PA-induced fibrinolysis of clots. Methods Turbidity is an accurate and convenient method, not previously used, to follow the effects of ultrasound. Deconvolution microscopy was used to determine changes in structure, while fluorescence recovery after photobleaching was used to characterize the kinetics of binding/unbinding and transport. Results The ultrasound pulse repetition frequency affected clot lysis times, but there were no thermal effects. Ultrasound in the absence of t-PA produced a slight but consistent decrease in turbidity, suggesting a decrease in fibrin diameter due solely to the action of the ultrasound, likely caused by an increase in protofibril tension because of vibration from ultrasound. Changes in fibrin network structure during lysis with ultrasound were visualized in real time by deconvolution microscopy, revealing that the network becomes unstable when 30–40% of the protein in the network was digested, whereas without ultrasound, the fibrin network was digested gradually and retained structural integrity. Fluorescence recovery after photobleaching during lysis revealed that the off-rate of oligomers from digesting fibers was not much affected but the number of binding/unbinding sites was increased. Conclusions Ultrasound causes a decrease in the diameter of the fibers due to tension as a result of vibration, leading to increased binding sites for plasmin(ogen)/t-PA. The positive feedback of this structural change together with increased mixing/transport of t-PA/plasmin(ogen) is likely to account for the observed enhancement of fibrinolysis by ultrasound. PMID:25619618

Potential effect of ultrasound on carbohydrates.

PubMed

Bera, Smritilekha; Mondal, Dhananjoy; Martin, Jacob T; Singh, Man

2015-06-17

The use of ultrasound has emerged as one of the most useful alternative energy sources for the synthesis of carbohydrate-derived biologically and pharmaceutically potential compounds. Spectacular advances have been made in the field of sonication-assisted organic reactions, which are known for producing superior yields, enhanced reactivity of the reactant, improved stereoselectivity, and shortened reaction times. Orthogonal protection-deprotection reactions and/or modification and manipulation of functional groups in carbohydrates are common synthetic steps in carbohydrate chemistry. These reaction steps can be driven by the ultrasonic energy generated by acoustic cavitation via the formation and subsequent collapse of ultrasound-induced bubbles. The ultrasound-assisted synthesis of differently functionalised monosaccharides is useful in a wide variety of applications of carbohydrate chemistry such as the glycosylation of oligosaccharides, one pot domino reactions, thioglycoside syntheses, azidoglycoside syntheses, 1,3-dipolar cycloaddition reactions, and syntheses of natural products. This review article covers ultrasound-mediated reactions on carbohydrates that have been described in the literature since 2000. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Application of ultrasound-enhanced gene and drug delivery to the ocular tissue].

PubMed

Sonoda, Shozo; Yamashita, Toshifumi; Suzuki, Ryo; Maruyama, Kazuo; Sakamoto, Taiji

2013-01-01

Visual images provide an immensely rich source of information about the external world. Eye has characteristic structure sensory cells are arranged along the eye wall, and is filled inside with vitreous body. In recent years, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent had widely spread, and numerous number of patients who suffered ocular angiogenic disease such as diabetic retinopathy, age-related macular degeneration and retinal vascular occlusion for the disease, were treated and spared the blindness. Vitreous cavity was regarded as reservoir of drug, intravitreal injection is thought a sort of drug delivery. However, with regard to the administration of a selective drug deliver, it has not yet been solved. Our aim is to establish a new method of gene transfer, drug delivery using low-energy ultrasound to the eye, to date, we confirmed drug and gene deliver to the ocular tissue such as cornea, conjunctiva and retina with high efficiency. In addition, tissue damage was minimal. We have also shown that ultrasound irradiation with combination of a microbubbles or bubble liposome could be introduced drug and gene more effectively. Based on these knowledge, we will focus on development of a new device for intraocular ultrasound exposure and potential for therapeutic application of ultrasound to humans retinal disease such as retinal artery obstruction.

Enhanced homing permeability and retention of bone marrow stromal cells (BMSC) by non-invasive pulsed focused ultrasound

PubMed Central

Ziadloo, Ali; Burks, Scott R.; Gold, Eric M.; Lewis, Bobbi K.; Chaudhry, Aneeka; Merino, Maria J.; Frenkel, Victor; Frank, Joseph A.

2012-01-01

Bone marrow stromal cells (BMSC) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically-administered cells, which results in low numbers of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients are present. We demonstrated that non-destructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSC were administered intravenously following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to 8 times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target BMSC homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of BMSC toward treated tissues. PMID:22593018

Cavitation enhances coagulated size during pulsed high-intensity focussed ultrasound ablation in an isolated liver perfusion system.

PubMed

Zhao, Lu-Yan; Liu, Shan; Chen, Zong-Gui; Zou, Jian-Zhong; Wu, Feng

2016-11-24

To investigate whether cavitation enhances the degree of coagulation during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver perfusion system. Isolated liver was treated by pulsed HIFU or continuous-wave HIFU with different portal vein flow rates. The cavitation emission during exposure was recorded, and real-time ultrasound images were used to observe changes in the grey scale. The coagulation size was measured and calculated. HIFU treatment led to complete coagulation necrosis and total cell destruction in the target regions. Compared to exposure at a duty cycle (DC) of 100%, the mean volumes of lesions induced by 6 s exposure at DCs of 50% and 10% were significantly larger (P < .01) but were smaller at a DC of 5%. The necrosis volume was negatively related to the perfusion rate in the pulsed HIFU at a DC of 50% for exposure durations of 4 and 6 s, while the perfusion flow rate did not affect the necrosis volume for exposure durations of 1, 2 and 3 s. For increased perfusion flow rates, there was no significant decrease in the cavitation activity for the pulsed-HIFU (P > .05). For continuous-wave HIFU exposure, there was a significant decrease in the necrosis volume and cavitation activity for exposure times of 1, 2, 3, 4, and 6 s with increasing portal perfusion rates. Perfusion flow rates negatively influence cavitation activity and coagulation volume. Ablation is significantly enhanced during pulsed HIFU exposure compared with continuous-wave HIFU.

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Ultrasound tissue analysis and characterization

NASA Astrophysics Data System (ADS)

Kaufhold, John; Chan, Ray C.; Karl, William C.; Castanon, David A.

1999-07-01

On the battlefield of the future, it may become feasible for medics to perform, via application of new biomedical technologies, more sophisticated diagnoses and surgery than is currently practiced. Emerging biomedical technology may enable the medic to perform laparoscopic surgical procedures to remove, for example, shrapnel from injured soldiers. Battlefield conditions constrain the types of medical image acquisition and interpretation which can be performed. Ultrasound is the only viable biomedical imaging modality appropriate for deployment on the battlefield -- which leads to image interpretation issues because of the poor quality of ultrasound imagery. To help overcome these issues, we develop and implement a method of image enhancement which could aid non-experts in the rapid interpretation and use of ultrasound imagery. We describe an energy minimization approach to finding boundaries in medical images and show how prior information on edge orientation can be incorporated into this framework to detect tissue boundaries oriented at a known angle.

Multifunctional microbubbles and nanobubbles for photoacoustic and ultrasound imaging

PubMed Central

Kim, Chulhong; Qin, Ruogu; Xu, Jeff S.; Wang, Lihong V.; Xu, Ronald

2010-01-01

We develop a novel dual-modal contrast agent—encapsulated-ink poly(lactic-co-glycolic acid) (PLGA) microbubbles and nanobubbles—for photoacoustic and ultrasound imaging. Soft gelatin phantoms with embedded tumor simulators of encapsulated-ink PLGA microbubbles and nanobubbles in various concentrations are clearly shown in both photoacoustic and ultrasound images. In addition, using photoacoustic imaging, we successfully image the samples positioned below 1.8-cm-thick chicken breast tissues. Potentially, simultaneous photoacoustic and ultrasound imaging enhanced by encapsulated-dye PLGA microbubbles or nanobubbles can be a valuable tool for intraoperative assessment of tumor boundaries and therapeutic margins. PMID:20210423

Motion Detection in Ultrasound Image-Sequences Using Tensor Voting

NASA Astrophysics Data System (ADS)

Inba, Masafumi; Yanagida, Hirotaka; Tamura, Yasutaka

2008-05-01

Motion detection in ultrasound image sequences using tensor voting is described. We have been developing an ultrasound imaging system adopting a combination of coded excitation and synthetic aperture focusing techniques. In our method, frame rate of the system at distance of 150 mm reaches 5000 frame/s. Sparse array and short duration coded ultrasound signals are used for high-speed data acquisition. However, many artifacts appear in the reconstructed image sequences because of the incompleteness of the transmitted code. To reduce the artifacts, we have examined the application of tensor voting to the imaging method which adopts both coded excitation and synthetic aperture techniques. In this study, the basis of applying tensor voting and the motion detection method to ultrasound images is derived. It was confirmed that velocity detection and feature enhancement are possible using tensor voting in the time and space of simulated ultrasound three-dimensional image sequences.

Assistive technology for ultrasound-guided central venous catheter placement.

PubMed

Ikhsan, Mohammad; Tan, Kok Kiong; Putra, Andi Sudjana

2018-01-01

This study evaluated the existing technology used to improve the safety and ease of ultrasound-guided central venous catheterization. Electronic database searches were conducted in Scopus, IEEE, Google Patents, and relevant conference databases (SPIE, MICCAI, and IEEE conferences) for related articles on assistive technology for ultrasound-guided central venous catheterization. A total of 89 articles were examined and pointed to several fields that are currently the focus of improvements to ultrasound-guided procedures. These include improving needle visualization, needle guides and localization technology, image processing algorithms to enhance and segment important features within the ultrasound image, robotic assistance using probe-mounted manipulators, and improving procedure ergonomics through in situ projections of important information. Probe-mounted robotic manipulators provide a promising avenue for assistive technology developed for freehand ultrasound-guided percutaneous procedures. However, there is currently a lack of clinical trials to validate the effectiveness of these devices.

Ultrasound contrast agent fabricated from microbubbles containing instant adhesives, and its ultrasound imaging ability

NASA Astrophysics Data System (ADS)

Makuta, T.; Tamakawa, Y.

2012-04-01

Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.

[Contrast-enhanced ultrasound for the characterization of incidental liver lesions - an economical evaluation in comparison with multi-phase computed tomography].

PubMed

Giesel, F L; Delorme, S; Sibbel, R; Kauczor, H-U; Krix, M

2009-06-01

The aim of the study was to conduct a cost-minimization analysis of contrast-enhanced ultrasound (CEUS) compared to multi-phase computed tomography (M-CT) as the diagnostic standard for diagnosing incidental liver lesions. Different scenarios of a cost-covering realization of CEUS in the ambulant sector in the general health insurance system of Germany were compared to the current cost situation. The absolute savings potential was estimated using different approaches for the calculation of the incidence of liver lesions which require further characterization. CEUS was the more cost-effective method in all scenarios in which CEUS examinations where performed at specialized centers (122.18-186.53 euro) compared to M-CT (223.19 euro). With about 40 000 relevant liver lesions per year, systematic implementation of CEUS would result in a cost savings of 4 m euro per year. However, the scenario of a cost-covering CEUS examination for all physicians who perform liver ultrasound would be the most cost-intensive approach (e. g., 407.87 euro at an average utilization of the ultrasound machine of 25 %, and a CEUS ratio of 5 %). A cost-covering realization of the CEUS method can result in cost savings in the German healthcare system. A centralized approach as proposed by the DEGUM should be targeted.

Enhanced cavitation and heating of flowing polymer- and lipid-shelled microbubbles and phase-shift nanodroplets during focused ultrasound exposures

NASA Astrophysics Data System (ADS)

Zhang, Siyuan; Cui, Zhiwei; Li, Chong; Zhou, Fanyu; Zong, Yujin; Wang, Supin; Wan, Mingxi

2017-03-01

Cavitation and heating are the primary mechanisms of numerous therapeutic applications of ultrasound. Various encapsulated microbubbles (MBs) and phase-shift nanodroplets (NDs) have been used to enhance local cavitation and heating, creating interests in developing ultrasound therapy using these encapsulated MBs and NDs. This work compared the efficiency of flowing polymer- and lipid-shelled MBs and phase-shift NDs in cavitation and heating during focused ultrasound (FUS) exposures. Cavitation activity and temperature were investigated when the solution of polymer- and lipid-shelled MBs and NDs flowed through the vessel in a tissue-mimicking phantom with varying flow velocities when exposed to FUS at various acoustic power levels. The inertial cavitation dose (ICD) for the encapsulated MBs and NDs were higher than those for the saline. Temperature initially increased with increasing flow velocities of the encapsulated MBs, followed by a decrease of the temperature with increasing flow velocities when the velocity was much higher. Meanwhile, ICD showed a trend of increases with increasing flow velocity. For the phase-shift NDs, ICD after the first FUS exposure was lower than those after the second FUS exposure. For the encapsulated MBs, ICD after the first FUS exposure was higher than those after the second FUS exposure. Further studies are necessary to investigate the treatment efficiency of different encapsulated MBs and phase-shift NDs in cavitation and heating.

Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

PubMed

Sheeran, Paul S; Rojas, Juan D; Puett, Connor; Hjelmquist, Jordan; Arena, Christopher B; Dayton, Paul A

2015-03-01

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties. To do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results indicate that droplets can produce contrast enhancement similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on formulation) and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also reports for the first time the ability to capture contrast washout kinetics of the target organ as a measure of vascular perfusion. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Comparison of Contrast-Enhanced Ultrasound and Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI for the Diagnosis of Macroscopic Type of Hepatocellular Carcinoma.

PubMed

Iwamoto, Takayuki; Imai, Yasuharu; Kogita, Sachiyo; Igura, Takumi; Sawai, Yoshiyuki; Fukuda, Kazuto; Yamaguchi, Yoshitaka; Matsumoto, Yasushi; Nakahara, Masanori; Morimoto, Osakuni; Seki, Yasushi; Ohashi, Hiroshi; Fujita, Norihiko; Kudo, Masatoshi; Takehara, Tetsuo

We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance. © 2016 S. Karger AG, Basel.

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

NASA Astrophysics Data System (ADS)

Pope, Ava G.; Wu, Gongting; McWhorter, Frances Y.; Merricks, Elizabeth P.; Nichols, Timothy C.; Czernuszewicz, Tomasz J.; Gallippi, Caterina M.; Oldenburg, Amy L.

2013-10-01

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg ml-1 Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of three-dimensional imaging of a 185 µL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi.

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound.

PubMed

Pope, Ava G; Wu, Gongting; McWhorter, Frances Y; Merricks, Elizabeth P; Nichols, Timothy C; Czernuszewicz, Tomasz J; Gallippi, Caterina M; Oldenburg, Amy L

2013-10-21

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg ml(-1) Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of three-dimensional imaging of a 185 µL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi.

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

PubMed Central

Pope, Ava G.; Wu, Gongting; McWhorter, Frances Y.; Merricks, Elizabeth C.; Nichols, Timothy C.; Czernuszewicz, Tomasz J.; Gallippi, Caterina M.; Oldenburg, Amy L.

2013-01-01

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg/ml Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of 3-dimensional imaging of a 185 μL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi. PMID:24077004

Ultrasound

MedlinePlus

Ultrasound is a type of imaging. It uses high-frequency sound waves to look at organs and ... liver, and other organs. During pregnancy, doctors use ultrasound to view the fetus. Unlike x-rays, ultrasound ...

Contrast-enhanced ultrasonography vs B-mode ultrasound for visualization of intima-media thickness and detection of plaques in human carotid arteries.

PubMed

Shah, Benoy N; Chahal, Navtej S; Kooner, Jaspal S; Senior, Roxy

2017-05-01

Carotid intima-media thickness (IMT) and plaque are recognized markers of increased risk for cerebrovascular events. Accurate visualization of the IMT and plaques is dependent upon image quality. Ultrasound contrast agents improve image quality during echocardiography-this study assessed whether contrast-enhanced ultrasound (CEUS) improves carotid IMT visualization and plaque detection in an asymptomatic population. Individuals free from known cardiovascular disease, enrolled in a community study, underwent B-mode and CEUS carotid imaging. Each carotid artery was divided into 10 segments (far and near walls of the proximal, mid and distal segments of the common carotid artery, the carotid bulb, and internal carotid artery). Visualization of the IMT complex and plaque assessments was made during both B-mode and CEUS imaging for all enrolled subjects, a total of 175 individuals (mean age 65±9 years). Visualization of the IMT was significantly improved during CEUS compared with B-mode imaging, in both near and far walls of the carotid arteries (% IMT visualization during B-mode vs CEUS imaging: 61% vs 94% and 66% vs 95% for right and left carotid arteries, respectively, P<.001 for both). Additionally, a greater number of plaques were detected during CEUS imaging compared with B-mode imaging (367 plaques vs 350 plaques, P=.02). Contrast-enhanced ultrasound improves visualization of the intima-media complex, in both near and far walls, of the common and internal carotid arteries and permits greater detection of carotid plaques. Further studies are required to determine whether there is incremental clinical and prognostic benefit related to superior plaque detection by CEUS. © 2017, Wiley Periodicals, Inc.

Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

PubMed

Lankford, Miles; Behm, Carolyn Z; Yeh, James; Klibanov, Alexander L; Robinson, Peter; Lindner, Jonathan R

2006-10-01

Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

Applications of Ultrasound in the Resection of Brain Tumors

PubMed Central

Sastry, Rahul; Bi, Wenya Linda; Pieper, Steve; Frisken, Sarah; Kapur, Tina; Wells, William; Golby, Alexandra J.

2016-01-01

Neurosurgery makes use of pre-operative imaging to visualize pathology, inform surgical planning, and evaluate the safety of selected approaches. The utility of pre-operative imaging for neuronavigation, however, is diminished by the well characterized phenomenon of brain shift, in which the brain deforms intraoperatively as a result of craniotomy, swelling, gravity, tumor resection, cerebrospinal fluid (CSF) drainage, and many other factors. As such, there is a need for updated intraoperative information that accurately reflects intraoperative conditions. Since 1982, intraoperative ultrasound has allowed neurosurgeons to craft and update operative plans without ionizing radiation exposure or major workflow interruption. Continued evolution of ultrasound technology since its introduction has resulted in superior imaging quality, smaller probes, and more seamless integration with neuronavigation systems. Furthermore, the introduction of related imaging modalities, such as 3-dimensional ultrasound, contrast-enhanced ultrasound, high-frequency ultrasound, and ultrasound elastography have dramatically expanded the options available to the neurosurgeon intraoperatively. In the context of these advances, we review the current state, potential, and challenges of intraoperative ultrasound for brain tumor resection. We begin by evaluating these ultrasound technologies and their relative advantages and disadvantages. We then review three specific applications of these ultrasound technologies to brain tumor resection: (1) intraoperative navigation, (2) assessment of extent of resection, and (3) brain shift monitoring and compensation. We conclude by identifying opportunities for future directions in the development of ultrasound technologies. PMID:27541694

FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

PubMed

Seiler, Gabriela S; Campbell, Nigel; Nixon, Britton; Tsuruta, James K; Dayton, Paul A; Jennings, Samuel; Redding, W Rich; Lustgarten, Meghann

2016-05-01

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. © 2016 American College of Veterinary Radiology.

Ultrasound

MedlinePlus Videos and Cool Tools

Ultrasound is a useful procedure for monitoring the baby's development in the uterus. Ultrasound uses inaudible sound waves to produce a two- ... sound waves and appear dark or black. An ultrasound can supply vital information about a mother's pregnancy ...

The growth of oscillating bubbles in an ultrasound field

NASA Astrophysics Data System (ADS)

Yamauchi, Risa; Yamashita, Tatsuya; Ando, Keita

2017-11-01

From our recent experiments to test particle removal by underwater ultrasound, dissolved gas supersaturation is found to play an important role in physical cleaning; cavitation bubble nucleation can be triggered easily by weak ultrasound under the supersaturation and mild motion of the bubbles contributes to efficient cleaning without erosion. The state of gas bubble nuclei in water is critical to the determination of a cavitation inception threshold. Under ultrasound forcing, the size of bubble nuclei is varied by the transfer of dissolved gas (i.e., rectified diffusion); the growth rate will be promoted by the supersaturation and is thus expected to contribute to cavitation activity enhancement. In the present work, we experimentally study rectified diffusion for bubbles attached at glass surfaces in an ultrasound field. We will present the evolution of bubble nuclei sizes with varying parameters such as dissolved oxygen supersaturation, and ultrasound intensity and frequency. the Research Grant of Keio Leading-edge Laboratory of Science & Technology.

Tumour Vascular Shutdown and Cell Death Following Ultrasound-Microbubble Enhanced Radiation Therapy

PubMed Central

El Kaffas, Ahmed; Gangeh, Mehrdad J.; Farhat, Golnaz; Tran, William Tyler; Hashim, Amr; Giles, Anoja; Czarnota, Gregory J.

2018-01-01

High-dose radiotherapy effects are regulated by acute tumour endothelial cell death followed by rapid tumour cell death instead of canonical DNA break damage. Pre-treatment with ultrasound-stimulated microbubbles (USMB) has enabled higher-dose radiation effects with conventional radiation doses. This study aimed to confirm acute and longitudinal relationships between vascular shutdown and tumour cell death following radiation and USMB in a wild type murine fibrosarcoma model using in vivo imaging. Methods: Tumour xenografts were treated with single radiation doses of 2 or 8 Gy alone, or in combination with low-/high-concentration USMB. Vascular changes and tumour cell death were evaluated at 3, 24 and 72 h following therapy, using high-frequency 3D power Doppler and quantitative ultrasound spectroscopy (QUS) methods, respectively. Staining using in situ end labelling (ISEL) and cluster of differentiation 31 (CD31) of tumour sections were used to assess cell death and vascular distributions, respectively, as gold standard histological methods. Results: Results indicated a decrease in the power Doppler signal of up to 50%, and an increase of more than 5 dBr in cell-death linked QUS parameters at 24 h for tumours treated with combined USMB and radiotherapy. Power Doppler and quantitative ultrasound results were significantly correlated with CD31 and ISEL staining results (p < 0.05), respectively. Moreover, a relationship was found between ultrasound power Doppler and QUS results, as well as between micro-vascular densities (CD31) and the percentage of cell death (ISEL) (R2 0.5-0.9). Conclusions: This study demonstrated, for the first time, the link between acute vascular shutdown and acute tumour cell death using in vivo longitudinal imaging, contributing to the development of theoretical models that incorporate vascular effects in radiation therapy. Overall, this study paves the way for theranostic use of ultrasound in radiation oncology as a diagnostic modality to

Ultrasound-modulated optical tomography with intense acoustic bursts.

PubMed

Zemp, Roger J; Kim, Chulhong; Wang, Lihong V

2007-04-01

Ultrasound-modulated optical tomography (UOT) detects ultrasonically modulated light to spatially localize multiply scattered photons in turbid media with the ultimate goal of imaging the optical properties in living subjects. A principal challenge of the technique is weak modulated signal strength. We discuss ways to push the limits of signal enhancement with intense acoustic bursts while conforming to optical and ultrasonic safety standards. A CCD-based speckle-contrast detection scheme is used to detect acoustically modulated light by measuring changes in speckle statistics between ultrasound-on and ultrasound-off states. The CCD image capture is synchronized with the ultrasound burst pulse sequence. Transient acoustic radiation force, a consequence of bursts, is seen to produce slight signal enhancement over pure ultrasonic-modulation mechanisms for bursts and CCD exposure times of the order of milliseconds. However, acoustic radiation-force-induced shear waves are launched away from the acoustic sample volume, which degrade UOT spatial resolution. By time gating the CCD camera to capture modulated light before radiation force has an opportunity to accumulate significant tissue displacement, we reduce the effects of shear-wave image degradation, while enabling very high signal-to-noise ratios. Additionally, we maintain high-resolution images representative of optical and not mechanical contrast. Signal-to-noise levels are sufficiently high so as to enable acquisition of 2D images of phantoms with one acoustic burst per pixel.

The Application of Ultrasound in 3D Bio-Printing.

PubMed

Zhou, Yufeng

2016-05-05

Three-dimensional (3D) bioprinting is an emerging and promising technology in tissue engineering to construct tissues and organs for implantation. Alignment of self-assembly cell spheroids that are used as bioink could be very accurate after droplet ejection from bioprinter. Complex and heterogeneous tissue structures could be built using rapid additive manufacture technology and multiple cell lines. Effective vascularization in the engineered tissue samples is critical in any clinical application. In this review paper, the current technologies and processing steps (such as printing, preparation of bioink, cross-linking, tissue fusion and maturation) in 3D bio-printing are introduced, and their specifications are compared with each other. In addition, the application of ultrasound in this novel field is also introduced. Cells experience acoustic radiation force in ultrasound standing wave field (USWF) and then accumulate at the pressure node at low acoustic pressure. Formation of cell spheroids by this method is within minutes with uniform size and homogeneous cell distribution. Neovessel formation from USWF-induced endothelial cell spheroids is significant. Low-intensity ultrasound could enhance the proliferation and differentiation of stem cells. Its use is at low cost and compatible with current bioreactor. In summary, ultrasound application in 3D bio-printing may solve some challenges and enhance the outcomes.

Ultrasound has synergistic effects in vitro with tirofiban and heparin for thrombus dissolution.

PubMed

Birnbaum, Y; Atar, S; Luo, H; Nagai, T; Siegel, R J

1999-12-15

Previous studies have shown synergism between ultrasound and thrombolytic agents or microbubbles on blood clot dissolution. It has not been investigated whether heparin or glycoprotein IIb/IIIa blockers enhance clot lysis by ultrasound. We compared the blood clot dissolution effect of saline, heparin, tissue plasminogen activator (tPA), tirofiban, and an echocardiographic contrast media (Optison) without and with ultrasound application. Human blood clots from four donors, 2 to 4 hours old, were cut into 200- to 400-mg sections, weighed, and immersed for 2 minutes in 1 L of normal saline 0.9% solution containing either heparin 1000 U, tirofiban 150 microg, tPA 20 mg, Optison 0.5 mL, or normal saline alone. Clots were randomized to 2 minutes ultrasound application or immersion alone without ultrasound. Ultrasound was applied with a 19.5 KHz catheter. After treatment, the clots were weighed, and the absolute and percent difference in weight was calculated. Immersion in heparin, tirofiban, and tPA without ultrasound did not augment clot disruption relative to normal saline alone. Immersion in Optison (p = 0.07) tended to result in less lysis than saline alone. Ultrasound enhanced clot dissolution compared to immersion alone with: saline (48.1+/-15.3% vs. 26.0+/-13.8%, p<0.0000002); heparin (60.8+/-17.5% vs. 30.8+/-15.1%, p = 0.000001); tirofiban (61.8+/-13.6% vs. 30.1+/-12.2%, p<0.0000001); tPA (53.1+/-15.3% vs. 30.2+/-11.5%, p<0.000002); and Optison (47.8+/-16.0% vs. 18.4+/-11.5%, p<0.0000001). The combination of tirofiban with ultrasound, as well as heparin with ultrasound, was associated with a significant augmentation of clot dissolution compared with the saline plus ultrasound group (p = 0.002, 0.013, respectively). Ultrasound with tPA or with Optison had no significant augmentation of clot dissolution over the ultrasound + saline effect. This in vitro study of catheter-delivered high-intensity low-frequency ultrasound demonstrates that: (1) tirofiban and heparin

Detection of tissue coagulation by decorrelation of ultrasonic echo signals in cavitation-enhanced high-intensity focused ultrasound treatment.

PubMed

Yoshizawa, Shin; Matsuura, Keiko; Takagi, Ryo; Yamamoto, Mariko; Umemura, Shin-Ichiro

2016-01-01

A noninvasive technique to monitor thermal lesion formation is necessary to ensure the accuracy and safety of high-intensity focused ultrasound (HIFU) treatment. The purpose of this study is to ultrasonically detect the tissue change due to thermal coagulation in the HIFU treatment enhanced by cavitation microbubbles. An ultrasound imaging probe transmitted plane waves at a center frequency of 4.5 MHz. Ultrasonic radio-frequency (RF) echo signals during HIFU exposure at a frequency of 1.2 MHz were acquired. Cross-correlation coefficients were calculated between in-phase and quadrature (IQ) data of two B-mode images with an interval time of 50 and 500 ms for the estimation of the region of cavitation and coagulation, respectively. Pathological examination of the coagulated tissue was also performed to compare with the corresponding ultrasonically detected coagulation region. The distribution of minimum hold cross-correlation coefficient between two sets of IQ data with 50-ms intervals was compared with a pulse inversion (PI) image. The regions with low cross-correlation coefficients approximately corresponded to those with high brightness in the PI image. The regions with low cross-correlation coefficients in 500-ms intervals showed a good agreement with those with significant change in histology. The results show that the regions of coagulation and cavitation could be ultrasonically detected as those with low cross-correlation coefficients between RF frames with certain intervals. This method will contribute to improve the safety and accuracy of the HIFU treatment enhanced by cavitation microbubbles.

[Contrast enhanced power Doppler and color Doppler ultrasound in breast masses: Efficiency in diagnosis and contributions to differential diagnosis].

PubMed

Algül, Ali; Balci, Pinar; Seçil, Mustafa; Canda, Tülay

2003-06-01

To compare ability of detection of vascular structures by utilizing ultrasonographic contrast agent (Levovist) prior to and following power Doppler ultrasound (PDUS) and colour Doppler ultrasound (CDUS) and to determine useful parameters in the differentiation of malignant and benign breast masses by means of verified data. Vascularisation characteristics of 38 breast masses (22 malignant, 16 benign) which were confirmed by mammography and B-mode sonography were evaluated by both CDUS and PDUS following and prior to intravenous contrast application. In addition, Vmax and RI values of vascular structures were calculated by Doppler spectral evaluation. Malignant lesions showed more vascularity than benign lesions both with and without contrast enhancement. With both methods, by utilizing contrast agent, central, penetrating and tortuous vascular structures became more significant in malignant lesions when compared with benign lesions. PDUS was able to detect vascular structures better than CDUS; however, the difference was not statistically significant. Presence of peripheral vascularity was not useful in differentiating malignant from benign lesions. Vmax and RI values were higher in malignant lesions and the difference was statistically significant. In both methods, Vmax > 15 cm/sec and RI > 0.80 (CDUS), and RI > 0.70 (PDUS) were accepted as malignancy parameters. Vascular patterns of breast masses as determined with PDUS and CDUS with contrast enhancement and Doppler spectral examinations enabled differentiation of malignant and benign breast lesions. Thus, it is possible to decrease the number of unnecessary surgical interventions.

Imaging Features on Contrast-Enhanced Ultrasound and Clinical Characteristics of Hepatitis B Virus-Related Combined Hepatocellular-Cholangiocarcinoma: Comparison with Hepatitis B Virus-Related Hepatocellular Carcinoma.

PubMed

Ye, Jieyi; Xie, Xiaoyan; Liu, Baoxian; Zhang, Xiaoer; Wang, Wei; Huang, Xiaowen; Lu, Mingde; Huang, Guangliang

2017-11-01

The objective of this study was to compare the clinical characteristics and imaging features on contrast-enhanced ultrasound (CEUS) of hepatitis B virus (HBV)-related combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC). Thirty-one pathologically proven CHCs were included and 31 HCCs were randomly selected as controls. Elevated carbohydrate antigen (CA) 19-9 alone and simultaneous elevation of α-fetoprotein and CA19-9 were more frequent in CHC than in HCC patients (p = 0.004 and 0.029, respectively). On CEUS, homogeneous, heterogeneous and peripheral irregular rim-like enhancement was illustrated in 8 (25.8%), 12 (38.7%) and 11 (35.5%) CHCs and in 6 (19.4%), 23 (74.1%) and 2 (6.5%) HCCs, respectively (p = 0.007). Multivariate logistic regression analysis revealed CA19-9 elevation (p = 0.011, odds ratio [OR] = 6.545) and peripheral irregular rim-like enhancement on CEUS (p = 0.017, OR = 7.718) were independent variables. A receiver operating characteristic curve was plotted and the area under the curve was 0.740. CHC should be watched for in HBV-infected patients with liver tumor manifesting peripheral irregular rim-like enhancement on CEUS, accompanied by CA19-9 elevation. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Nonlinear acoustics in biomedical ultrasound

NASA Astrophysics Data System (ADS)

Cleveland, Robin O.

2015-10-01

Ultrasound is widely used to image inside the body; it is also used therapeutically to treat certain medical conditions. In both imaging and therapy applications the amplitudes employed in biomedical ultrasound are often high enough that nonlinear acoustic effects are present in the propagation: the effects have the potential to be advantageous in some scenarios but a hindrance in others. In the case of ultrasound imaging the nonlinearity produces higher harmonics that result in images of greater quality. However, nonlinear effects interfere with the imaging of ultrasound contrast agents (typically micron sized bubbles with a strong nonlinear response of their own) and nonlinear effects also result in complications when derating of pressure measurements in water to in situ values in tissue. High intensity focused ultrasound (HIFU) is emerging as a non-invasive therapeutic modality which can result in thermal ablation of tissue. For thermal ablation, the extra effective attenuation resulting from nonlinear effects can result in enhanced heating of tissue if shock formation occurs in the target region for ablation - a highly desirable effect. However, if nonlinearity is too strong it can also result in undesired near-field heating and reduced ablation in the target region. The disruption of tissue (histotripsy) and fragmentation of kidney stones (lithotripsy) exploits shock waves to produce mechanically based effects, with minimal heating present. In these scenarios it is necessary for the waves to be of sufficient amplitude that a shock exists when the waveform reaches the target region. This talk will discuss how underlying nonlinear phenomenon act in all the diagnostic and therapeutic applications described above.

Ultrasound of the small joints of the hands and feet: current status

PubMed Central

2007-01-01

The aim of this article was to review the current status of ultrasound imaging of patients with rheumatological disorders of the hands and feet. Ultrasound machines with high-resolution surface probes are readily available in most radiology departments and can be used to address important clinical questions posed by the rheumatologist and sports and rehabilitation physician. There is increasing evidence that ultrasound detects synovitis that is silent to clinical examination. Detection and classification of synovitis and the early detection of bone erosions are important in clinical decision making. Ultrasound has many advantages over other imaging techniques with which it is compared, particularly magnetic resonance. The ability to carry out a rapid assessment of many widely spaced joints, coupled with clinical correlation, the ability to move and stress musculoskeletal structures and the use of ultrasound to guide therapy accurately are principal amongst these. The use of colour flow Doppler studies provides a measure of neovascularisation within the synovial lining of joints and tendons, and within tendons themselves, that is not available with other imaging techniques. Disadvantages compared to MRI include small field of view, poor image presentation, and difficulty in demonstrating cartilage and deep joints in their entirety. Contrast-enhanced magnetic resonance provides a better measure of capillary permeability and extracellular fluid than does ultrasound. The ability to image simultaneously multiple small joints in the hands and feet and their enhancement characteristics cannot be matched with ultrasound, though future developments in 3-D ultrasound may narrow this gap. Magnetic resonance provides a more uniform and reproducible image for long-term follow-up studies. PMID:17712556

Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

PubMed

Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

2014-01-01

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Models of temporal enhanced ultrasound data for prostate cancer diagnosis: the impact of time-series order

NASA Astrophysics Data System (ADS)

Nahlawi, Layan; Goncalves, Caroline; Imani, Farhad; Gaed, Mena; Gomez, Jose A.; Moussa, Madeleine; Gibson, Eli; Fenster, Aaron; Ward, Aaron D.; Abolmaesumi, Purang; Mousavi, Parvin; Shatkay, Hagit

2017-03-01

Recent studies have shown the value of Temporal Enhanced Ultrasound (TeUS) imaging for tissue characterization in transrectal ultrasound-guided prostate biopsies. Here, we present results of experiments designed to study the impact of temporal order of the data in TeUS signals. We assess the impact of variations in temporal order on the ability to automatically distinguish benign prostate-tissue from malignant tissue. We have previously used Hidden Markov Models (HMMs) to model TeUS data, as HMMs capture temporal order in time series. In the work presented here, we use HMMs to model malignant and benign tissues; the models are trained and tested on TeUS signals while introducing variation to their temporal order. We first model the signals in their original temporal order, followed by modeling the same signals under various time rearrangements. We compare the performance of these models for tissue characterization. Our results show that models trained over the original order-preserving signals perform statistically significantly better for distinguishing between malignant and benign tissues, than those trained on rearranged signals. The performance degrades as the amount of temporal-variation increases. Specifically, accuracy of tissue characterization decreases from 85% using models trained on original signals to 62% using models trained and tested on signals that are completely temporally-rearranged. These results indicate the importance of order in characterization of tissue malignancy from TeUS data.

Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling.

PubMed

Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi

2016-12-01

Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Mu, Zhaomei; Ma, C.-M.; Chen, Xiaoming; Cvetkovic, Dusica; Pollack, Alan; Chen, Lili

2012-01-01

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS (5) docetaxel + RT (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg-1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio.

Comparison of transcutaneous contrast-enhanced ultrasound-guided injected hemostatic agents with traditional surgery treatment for liver, spleen and kidney trauma: a retrospective study.

PubMed

Wang, Dong; Lv, Faqin; Luo, Yukun; An, Lichun; Li, Junlai; Xie, Xia; Tian, Jiangke; Zhao, Weiyan; Tang, Jie

2012-10-01

There is lack of studies on the effectiveness of transcutaneous contrast-enhanced ultrasound-guided injections of hemostatic agents for liver. spleen and kidney trauma. We compared treatment by hemostatic agents to surgical treatment in a retrospective interventional human study. The study enrolled a total of 135 subjects from emergency unit of the Chinese People's Liberation Army General Hospital in Beijing. Within the cohort, 62 patients received contrast enhanced ultrasound-guided injection of hemostatic agents and the rest received surgical treatments. The injury severity score was lower in the hemostatic agent treatment group than surgical treatment group (p<0.05), but Glasgow coma scale scores did not reach statistical significance. The patients in the surgical treatment group had significantly higher hospital fees than those in the hemostatic treatment group (p<0.05), although the length of hospitalization did not significantly differ between two groups. Safety outcome variables pre- and post-treatment remained within normal limits in both groups. Hemostatic agents were more cost-effective than surgery to treat patients with liver, spleen and kidney trauma. However, given the limited sample size, subsequent studies drawing upon larger populations from multiple medical centers are necessary for follow-up.

Blood-Brain Barrier Disruption Caused by Ultrasound Bursts Combined with Microbubbles Depends on Anesthesia

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2011-09-01

Prior works on BBB disruption via inter-arterial infusions of osmotic agents have shown a strong dependence on anesthesia. Here, we investigated whether different anesthesia agents can affect ultrasound-induced BBB disruption. A piston transducer fired through a rubber aperture (frequency: 532 kHz, diameter: 4 cm, aperture diameter: 16 mm) was used to generate the ultrasound fields, and sonications combined with an ultrasound contrast agent were performed at 5 power levels. BBB disruption was quantified by measuring the MRI contrast enhancement in T1-weighted MRI, and erythrocyte extravasation characterized in light microscopy. For each exposure level tested, experiments performed with ketamine/xylazine resulted in significantly greater (P<0.05) enhancement than with isoflurane/oxygen. The onset of severe red blood cell extravasation occurred at lower power levels with ketamine/xylazine. These results suggest ultrasound-induced BBB disruption can depend on anesthesia agent, possibly due effects on the vasculature. These results suggest that care is needed in comparing experiments with different anesthesia agents and physiological factors need to be considered with ultrasound-induced BBB disruption.

Phase-space topography characterization of nonlinear ultrasound waveforms.

PubMed

Dehghan-Niri, Ehsan; Al-Beer, Helem

2018-03-01

Fundamental understanding of ultrasound interaction with material discontinuities having closed interfaces has many engineering applications such as nondestructive evaluation of defects like kissing bonds and cracks in critical structural and mechanical components. In this paper, to analyze the acoustic field nonlinearities due to defects with closed interfaces, the use of a common technique in nonlinear physics, based on a phase-space topography construction of ultrasound waveform, is proposed. The central idea is to complement the "time" and "frequency" domain analyses with the "phase-space" domain analysis of nonlinear ultrasound waveforms. A nonlinear time series method known as pseudo phase-space topography construction is used to construct equivalent phase-space portrait of measured ultrasound waveforms. Several nonlinear models are considered to numerically simulate nonlinear ultrasound waveforms. The phase-space response of the simulated waveforms is shown to provide different topographic information, while the frequency domain shows similar spectral behavior. Thus, model classification can be substantially enhanced in the phase-space domain. Experimental results on high strength aluminum samples show that the phase-space transformation provides a unique detection and classification capabilities. The Poincaré map of the phase-space domain is also used to better understand the nonlinear behavior of ultrasound waveforms. It is shown that the analysis of ultrasound nonlinearities is more convenient and informative in the phase-space domain than in the frequency domain. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiparametric dynamic contrast-enhanced ultrasound imaging of prostate cancer.

PubMed

Wildeboer, Rogier R; Postema, Arnoud W; Demi, Libertario; Kuenen, Maarten P J; Wijkstra, Hessel; Mischi, Massimo

2017-08-01

The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. The combination of the spatiotemporal correlation (r), mean transit time (μ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), μ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

PubMed

Tsao, Nadia H; Hall, Elizabeth A H

2017-11-14

Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for decolorization of azo dye.

PubMed

Huang, Tianyin; Zhang, Ke; Qian, Yajie; Fang, Cong; Chen, Jiabin

2018-02-20

Activated carbon fiber (ACF) has become an emerging activator for peroxydisulfate (PDS) to generate sulfate radical (SO 4 •- ). However, the relative low activation efficiency and poor contaminant mineralization limited its widespread application. Herein, ultrasound (US) was introduced to the ACF activated PDS system, and the synergistic effect of US and ACF in PDS activation and the enhancement of contaminant mineralization were investigated. The synergistic effect of US and ACF was observed in the PDS activation to decolorize orange G (OG). The decolorization efficiency increased with increasing ACF loading and US power, and PDS/OG ratio from 1 to 40. The activation energy was determined to be 24.065 kJ/mol. The radical-induced decolorization of OG took place on the surface of ACF, and both SO 4 •- and hydroxyl radical ( • OH) contributed to OG decolorization. The azo bond and naphthalene ring on OG were destructed to other aromatic intermediates and finally mineralized to CO 2 and H 2 O. The introduction of US in the ACF/PDS system significantly enhanced the mineralization of OG. The combination of US and PDS was highly efficient to activate PDS to decolorize azo dyes. Moreover, the introduction of US remarkably improved the contaminant mineralization.

Influence of ageing on quantitative contrast-enhanced ultrasound of the kidneys in healthy cats.

PubMed

Stock, Emmelie; Paepe, Dominique; Daminet, Sylvie; Duchateau, Luc; Saunders, Jimmy H; Vanderperren, Katrien

2018-05-05

The degenerative effects of ageing on the kidneys have been extensively studied in humans. However, only recently interest has been focused on renal ageing in veterinary medicine. Contrast-enhanced ultrasound allows non-invasive evaluation of renal perfusion in conscious cats. Renal perfusion parameters were obtained in 43 healthy cats aged 1-16 years old, and the cats were divided in four age categories: 1-3 years, 3-6 years, 6-10 years and over 10 years. Routine renal parameters as serum creatinine, serum urea, urine-specific gravity, urinary protein:creatinine ratio and systolic blood pressure were also measured. No significant differences in any of the perfusion parameters were observed among the different age categories. A trend towards a lower peak enhancement and wash-in area under the curve with increasing age, suggestive for a lower blood volume, was detected when comparing the cats over 10 years old with the cats of 1-3 years old. Additionally, no significant age-effect was observed for the serum and urine parameters, whereas a higher blood pressure was observed in healthy cats over 10 years old. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SURGE: Smart Ultrasound Remote Guidance Experiment

NASA Technical Reports Server (NTRS)

Peterson, Sean

2009-01-01

Exploration-class missions lead to longer communication delays with mission control. May not always have communication capability to stream real-time ultrasound images. SURGE explores use of a "just-in-time" learning tool, called OPEL = On-Board Proficiency Enhancer Light as an aid to a hypothetical crew medical officer working autonomously.

A brief history of ultrasound in rheumatology: where we were.

PubMed

Grassi, Walter; Filippucci, Emilio

2014-01-01

Ultrasonography in the '70s was a well-known and widely used method within several medical specialties but not in rheumatology. Initial development of the field was led by radiologists who mainly investigated the potential of ultrasound in the assessment of large joints. In the late '80s, the first studies supporting the role of ultrasound in the detection of soft tissue changes and bone erosions in the hands of patients with rheumatoid arthritis were published. In the '90s, the dramatic improvement of spatial resolution due to the new generation high frequency probes opened up new avenues for the exploration of otherwise undetectable anatomical details. Ultrasound research during this period was enhanced by the growing use of colour Doppler and power Doppler and by the first prototypes of three dimensional ultrasound. Over the last 10 years, the buzz words in ultrasound research in rheumatology have been standardisation, early diagnosis and therapy monitoring.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

PubMed

Li, Hongbo; Yang, Yanye; Zhang, Meimei; Yin, Liping; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2018-05-01

synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver. © 2017 by the American Institute of Ultrasound in Medicine.

Nanoparticle Delivery Enhancement With Acoustically Activated Microbubbles

PubMed Central

Mullin, Lee B; Phillips, Linsey C; Dayton, Paul A

2013-01-01

The application of microbubbles and ultrasound to deliver nanoparticle carriers for drug and gene delivery is an area that has expanded greatly in recent years. Under ultrasound exposure, microbubbles can enhance nanoparticle delivery by increasing cellular and vascular permeability. In this review, the underlying mechanisms of enhanced nanoparticle delivery with ultrasound and microbubbles and various proposed delivery techniques are discussed. Additionally, types of nanoparticles currently being investigated in preclinical studies, as well as the general limitations and benefits of a microbubble-based approach to nanoparticle delivery are reviewed. PMID:23287914

A review on lipase-catalyzed reactions in ultrasound-assisted systems.

PubMed

Lerin, Lindomar A; Loss, Raquel A; Remonatto, Daniela; Zenevicz, Mara Cristina; Balen, Manuela; Netto, Vendelino Oenning; Ninow, Jorge L; Trentin, Cláudia M; Oliveira, J Vladimir; de Oliveira, Débora

2014-12-01

The named "green chemistry" has been receiving increasing prominence due to its environmentally friendly characteristics. The use of enzymes as catalysts in processes of synthesis to replace the traditional use of chemical catalysts present as main advantage the fact of following the principles of the green chemistry. However, processes of enzymatic nature generally provide lower yields when compared to the conventional chemical processes. Therefore, in the last years, the ultrasound has been extensively used in enzymatic processes, such as the production of esters with desirable characteristics for the pharmaceutical, cosmetics, and food industry, for the hydrolysis and glycerolysis of vegetable oils, production of biodiesel, etc. Several works found in the open literature suggest that the energy released by the ultrasound during the cavitation phenomena can be used to enhance mass transfer (substrate/enzyme), hence increasing the rate of products formation, and also contributing to enhance the enzyme catalytic activity. Furthermore, the ultrasound is considered a "green" technology due to its high efficiency, low instrumental requirement and significant reduction of the processing time in comparison to other techniques. The main goal of this review was to summarize studies available to date regarding the application of ultrasound in enzyme-catalyzed esterification, hydrolysis, glycerolysis and transesterification reactions.

Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

PubMed

Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

2016-01-01

We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P <  0.05. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

PubMed

Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of therapeutic ultrasound on the nucleus and genomic DNA.

PubMed

Furusawa, Yukihiro; Hassan, Mariame A; Zhao, Qing-Li; Ogawa, Ryohei; Tabuchi, Yoshiaki; Kondo, Takashi

2014-11-01

In recent years, data have been accumulating on the ability of ultrasound to affect at a distance inside the cell. Previous conceptions about therapeutic ultrasound were mainly based on compromising membrane permeability and triggering some biochemical reactions. However, it was shown that ultrasound can access deep to the nuclear territory resulting in enhanced macromolecular localization as well as alterations in gene and protein expression. Recently, we have reported on the occurrence of DNA double-strand breaks in different human cell lines exposed to ultrasound in vitro with some insight into the subsequent DNA damage response and repair pathways. The impact of these observed effects again sways between extremes. It could be advantageous if employed in gene therapy, wound and bone fracture-accelerated healing to promote cellular proliferation, or in cancer eradication if the DNA lesions would culminate in cell death. However, it could be a worrying sign if they were penultimate to further cellular adaptations to stresses and thus shaking the safety of ultrasound application in diagnosis and therapy. In this review, an overview of the rationale of therapeutic ultrasound and the salient knowledge on ultrasound-induced effects on the nucleus and genomic DNA will be presented. The implications of the findings will be discussed hopefully to provide guidance to future ultrasound research. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.

PubMed

Colen, Rivka R; Sahnoune, Iman; Weinberg, Jeffrey S

2017-10-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules. Copyright © 2017 Elsevier Inc. All rights reserved.

Nanobubble Ultrasound Contrast Agents for Enhanced Delivery of Thermal Sensitizer to Tumors Undergoing Radiofrequency Ablation

PubMed Central

Perera, Reshani H.; Solorio, Luis; Wu, Hanping; Gangolli, Mihika; Silverman, Eric; Hernandez, Christopher; Peiris, Pubudu M.; Broome, Ann-Marie

2013-01-01

Purpose Pluronic has been shown to sensitize various tumor cell lines to chemotherapy and hyperthermia by altering the membrane fluidity, depleting ATP, and modulating the heat shock protein 70 expression. In our prior work, Pluronic was also used to formulate nanosized ultrasound contrast agents. In the current study we evaluate the use of these contrast agents as vehicles for image-guided delivery of Pluronic to improve outcomes of tumor radiofrequency (RF) ablation. Methods Lipid-shelled Pluronic nanobubbles were prepared and examined for size distribution, zeta potential, stability, biodistribution, accumulation of nanobubbles in the tumor, and treatment efficacy. LS174-T xenograft tumor-bearing mice were used to evaluate tumor growth suppression and measure treatment efficacy after RF ablation. Results The average diameter of Pluronic bubbles was 230 nm, and initial bubble echogenicity was 16 dB. In vitro, cells exposed to Pluronic nanobubbles exhibited low cytotoxicity in the absence of ultrasound, even if heat (43°C) was applied. When the cells were exposed to Pluronic nanobubbles, heat, and ultrasound; viability was significantly reduced. In vivo, tumors treated with ultrasound-modulated nanobubbles prior to RF ablation showed a significant reduction in growth compared to the RF alone (P<0.05). Conclusion Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation. PMID:23943542

Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation.

PubMed

Perera, Reshani H; Solorio, Luis; Wu, Hanping; Gangolli, Mihika; Silverman, Eric; Hernandez, Christopher; Peiris, Pubudu M; Broome, Ann-Marie; Exner, Agata A

2014-06-01

Pluronic has been shown to sensitize various tumor cell lines to chemotherapy and hyperthermia by altering the membrane fluidity, depleting ATP, and modulating the heat shock protein 70 expression. In our prior work, Pluronic was also used to formulate nanosized ultrasound contrast agents. In the current study we evaluate the use of these contrast agents as vehicles for image-guided delivery of Pluronic to improve outcomes of tumor radiofrequency (RF) ablation. Lipid-shelled Pluronic nanobubbles were prepared and examined for size distribution, zeta potential, stability, biodistribution, accumulation of nanobubbles in the tumor, and treatment efficacy. LS174-T xenograft tumor-bearing mice were used to evaluate tumor growth suppression and measure treatment efficacy after RF ablation. The average diameter of Pluronic bubbles was 230 nm, and initial bubble echogenicity was 16 dB. In vitro, cells exposed to Pluronic nanobubbles exhibited low cytotoxicity in the absence of ultrasound, even if heat (43 ºC) was applied. When the cells were exposed to Pluronic nanobubbles, heat, and ultrasound; viability was significantly reduced. In vivo, tumors treated with ultrasound-modulated nanobubbles prior to RF ablation showed a significant reduction in growth compared to the RF alone (P<0.05). Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation.

Semi-automatic motion compensation of contrast-enhanced ultrasound images from abdominal organs for perfusion analysis.

PubMed

Schäfer, Sebastian; Nylund, Kim; Sævik, Fredrik; Engjom, Trond; Mézl, Martin; Jiřík, Radovan; Dimcevski, Georg; Gilja, Odd Helge; Tönnies, Klaus

2015-08-01

This paper presents a system for correcting motion influences in time-dependent 2D contrast-enhanced ultrasound (CEUS) images to assess tissue perfusion characteristics. The system consists of a semi-automatic frame selection method to find images with out-of-plane motion as well as a method for automatic motion compensation. Translational and non-rigid motion compensation is applied by introducing a temporal continuity assumption. A study consisting of 40 clinical datasets was conducted to compare the perfusion with simulated perfusion using pharmacokinetic modeling. Overall, the proposed approach decreased the mean average difference between the measured perfusion and the pharmacokinetic model estimation. It was non-inferior for three out of four patient cohorts to a manual approach and reduced the analysis time by 41% compared to manual processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrasound - Breast

MedlinePlus

... the patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... perform an ultrasound-guided biopsy . Because ultrasound provides real-time images, it is often used to guide biopsy ...

Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate

PubMed Central

Lopez, Renata F.V.; Seto, Jennifer E.; Blankschtein, Daniel; Langer, Robert

2010-01-01

The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively-coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ~0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500–1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. PMID:20971504

Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate.

PubMed

Lopez, Renata F V; Seto, Jennifer E; Blankschtein, Daniel; Langer, Robert

2011-01-01

The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ∼0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500-1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. Copyright © 2010 Elsevier Ltd. All rights reserved.

Obstetric Ultrasound

PubMed Central

Nicholson, Stuart F.; Nimrod, Carl A.

1988-01-01

This article addresses the current indications for an obstetric ultrasound and describes the findings that it is reasonable to expect when reading an ultrasound report. The authors discuss several common obstetrical problems focussing the attention on the usefulness of the imaging information. Finally, they provide a glimpse into the future direction of obstetric ultrasound by discussing vaginal scanning, Doppler assessment of fetal blood flow, and routine ultrasound in pregnancy. PMID:21253229

Sonothrombolysis of Intra-Catheter Aged Venous Thrombi Using Microbubble Enhancement and Guided Three Dimensional Ultrasound Pulses

PubMed Central

Kutty, Shelby; Xie, Feng; Gao, Shunji; Drvol, Lucas K; Lof, John; Fletcher, Scott E; Radio, Stanley J; Danford, David A; Hammel, James M; Porter, Thomas R

2010-01-01

Central venous and arterial catheters are a major source of thrombo-embolic disease in children. We hypothesized that guided high mechanical index (MI) impulses from diagnostic three-dimensional (3D) ultrasound during an intravenous microbubble infusion could dissolve these thrombi. An in vitro system simulating intra-catheter thrombi was created and then treated with guided high MI impulses from 3D ultrasound, utilizing low MI microbubble sensitive imaging pulse sequence schemes to detect the microbubbles (Perflutren Lipid Microsphere, Definity®, Lantheus). Ten aged thrombi over 24 hours old were tested using 3D ultrasound coupled with a continuous diluted microbubble infusion (Group A), and ten with 3D ultrasound alone (Group B). Mean thrombus age was 28.6 hours (range 26.6–30.3). Groups A exhibited a 55 ± 19 % reduction in venous thrombus size, compared to 31±10 % for Group B (p=0.008). Feasibility testing was performed in 4 pigs, establishing a model to further investigate the efficacy. Sonothrombolysis of aged intra-catheter venous thrombi can be achieved with commercially available microbubbles and guided high MI ultrasound from a diagnostic 3D transducer. PMID:20696549

The Role of Acoustic Cavitation in Ultrasound-triggered Drug Release from Echogenic Liposomes

NASA Astrophysics Data System (ADS)

Kopechek, Jonathan A.

Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. CVD-related mortality, including coronary heart disease, heart failure, or stroke, generally occurs due to atherosclerosis, a condition in which plaques build up within arterial walls, potentially causing blockage or rupture. Targeted therapies are needed to achieve more effective treatments. Echogenic liposomes (ELIP), which consist of a lipid membrane surrounding an aqueous core, have been developed to encapsulate a therapeutic agent and/or gas bubbles for targeted delivery and ultrasound image enhancement. Under certain conditions ultrasound can cause nonlinear bubble growth and collapse, known as "cavitation." Cavitation activity has been associated with enhanced drug delivery across cellular membranes. However, the mechanisms of ultrasound-mediated drug release from ELIP have not been previously investigated. Thus, the objective of this dissertation is to elucidate the role of acoustic cavitation in ultrasound-mediated drug release from ELIP. To determine the acoustic and physical properties of ELIP, the frequency-dependent attenuation and backscatter coefficients were measured between 3 and 30 MHz. The results were compared to a theoretical model by measuring the ELIP size distribution in order to determine properties of the lipid membrane. It was found that ELIP have a broad size distribution and can provide enhanced ultrasound image contrast across a broad range of clinically-relevant frequencies. Calcein, a hydrophilic fluorescent dye, and papaverine, a lipophilic vasodilator, were separately encapsulated in ELIP and exposed to color Doppler ultrasound pulses from a clinical diagnostic ultrasound scanner in a flow system. Spectrophotometric techniques (fluorescence and absorbance measurements) were used to detect calcein or papaverine release. As a positive control, Triton X-100 (a non-ionic detergent) was added to ELIP samples not exposed to ultrasound in order

Ultrasound assisted intensification of enzyme activity and its properties: a mini-review.

PubMed

Nadar, Shamraja S; Rathod, Virendra K

2017-08-22

Over the last decade, ultrasound technique has emerged as the potential technology which shows large applications in food and biotechnology processes. Earlier, ultrasound has been employed as a method of enzyme inactivation but recently, it has been found that ultrasound does not inactivate all enzymes, particularly, under mild conditions. It has been shown that the use of ultrasonic treatment at appropriate frequencies and intensity levels can lead to enhanced enzyme activity due to favourable conformational changes in protein molecules without altering its structural integrity. The present review article gives an overview of influence of ultrasound irradiation parameters (intensity, duty cycle and frequency) and enzyme related factors (enzyme concentration, temperature and pH) on the catalytic activity of enzyme during ultrasound treatment. Also, it includes the effect of ultrasound on thermal kinetic parameters and Michaelis-Menten kinetic parameters (k m and V max ) of enzymes. Further, in this review, the physical and chemical effects of ultrasound on enzyme have been correlated with thermodynamic parameters (enthalpy and entropy). Various techniques used for investigating the conformation changes in enzyme after sonication have been highlighted. At the end, different techniques of immobilization for ultrasound treated enzyme have been summarized.

Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy of the Neonatal Bowel: Novel, Bedside, Noninvasive, and Radiation-Free Imaging for Early Detection of Necrotizing Enterocolitis.

PubMed

Al-Hamad, Suzanne; Hackam, David J; Goldstein, Seth D; Huisman, Thierry A G M; Darge, Kassa; Hwang, Misun

2018-05-31

Despite extensive research and improvements in the field of neonatal care, the morbidity and mortality associated with necrotizing enterocolitis (NEC) have remained unchanged over the past three decades. Early detection of ischemia and necrotic bowel is vital in improving morbidity and mortality associated with NEC; however, strategies for predicting and preventing NEC are lacking. Contrast-enhanced ultrasound (CEUS) and near-infrared spectroscopy (NIRS) are novel techniques in pediatrics that have been proven as safe modalities. CEUS has benefits over conventional ultrasound (US) by its improved real-time evaluation of the micro- and macrovascularities of normally and abnormally perfused tissue. US has been implemented as a useful adjunct to X-ray for earlier evaluation of NEC. NIRS is another noninvasive technique that has shown promise in improving early detection of NEC. The purpose of this article is to review the current understanding of changes in bowel perfusion in NEC, discuss the accuracy of abdominal US in detecting NEC, and explain how the use of CEUS and NIRS will enhance the precise and early detection of altered/pathological bowel wall perfusion in the initial development and course of NEC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound

PubMed Central

Brückner, Markus; Heidemann, Jan; Nowacki, Tobias M; Cordes, Friederike; Stypmann, Jörg; Lenz, Philipp; Gohar, Faekah; Lügering, Andreas; Bettenworth, Dominik

2017-01-01

AIM To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss (r2 = 0.74) and histological damage (r2 = 0.86) (P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAdCAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 dB ± 1.6 vs 12.9 dB ± 1.4 vs 18 dB ± 3.33, P < 0.05). Employing the AOM/DSS-induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa (healthy mucosa, 1.6 dB ± 1.4 vs 42 d, 18.2 dB ± 3.3 vs 84 d, 18.6 dB ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound.

PubMed

Brückner, Markus; Heidemann, Jan; Nowacki, Tobias M; Cordes, Friederike; Stypmann, Jörg; Lenz, Philipp; Gohar, Faekah; Lügering, Andreas; Bettenworth, Dominik

2017-04-28

To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss ( r 2 = 0.74) and histological damage ( r 2 = 0.86) ( P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAdCAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 dB ± 1.6 vs 12.9 dB ± 1.4 vs 18 dB ± 3.33, P < 0.05). Employing the AOM/DSS-induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa (healthy mucosa, 1.6 dB ± 1.4 vs 42 d, 18.2 dB ± 3.3 vs 84 d, 18.6 dB ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings (VEGF

Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: its application to targeted sonodynamic therapy.

PubMed

Ninomiya, Kazuaki; Noda, Kyohei; Ogino, Chiaki; Kuroda, Shun-ichi; Shimizu, Nobuaki

2014-01-01

The present study demonstrated the enhanced hydroxyl (OH) radical generation by combined use of dual-frequency (0.5 MHz and 1 MHz) ultrasound (US) and titanium dioxide (TiO2) nanoparticles (NPs) as sonocatalyst. The OH radical generation became the maximum, when 0.5 MHz US was irradiated at an intensity of 0.8 W/cm(2) and 1 MHz US was irradiated at intensities at 0.4 W/cm(2) in the presence of TiO2 NPs under the examined conditions. After incorporation of TiO2 NPs modified with targeting protein pre-S1/S2, HepG2 cancer cells were subjected to the dual-frequency US at optimum irradiation intensities ("targeted-TiO2/dual-US treatment"). Growth of the HepG2 cells was reduced by 46% compared with the control condition after irradiation of dual-frequency US for 60s with TiO2 NPs incorporation. In contrast, HepG2 cell growth was almost the same as that in the control condition when cells were irradiated with either 0.5 MHz or 1 MHz ultrasound alone without TiO2 NP incorporation. Copyright © 2013 Elsevier B.V. All rights reserved.

Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.

PubMed

Apfelbeck, M; Clevert, D-A; Ricke, J; Stief, C; Schlenker, B

2018-01-01

Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

PubMed

Reitmeir, Raluca; Eyding, Jens; Oertel, Markus F; Wiest, Roland; Gralla, Jan; Fischer, Urs; Giquel, Pierre-Yves; Weber, Stefan; Raabe, Andreas; Mattle, Heinrich P; Z'Graggen, Werner J; Beck, Jürgen

2017-04-01

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson's chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

WE-A-18C-01: Emerging and Innovative Ultrasound Technology in Diagnosis and Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emelianov, S; Oraevsky, A; Stafford, R

The application of new ultrasound-based technologies in medicine has expanded in recent years. One area of rapid growth has been the combination of ultrasound with other methods of image generation and imaging modalities to produce hybrid approaches for diagnostic imaging and noninvasive therapeutic intervention. The presentations associated with this session will provide an overview of two emerging technologies that are currently being developed and implemented to enhance ultrasound-related diagnostic imaging and therapy: the utilization of optically-induced ultrasound imaging (optoacoustic / photoacoustic imaging) and the use of magnetic resonance imaging to guide the use of high-intensity focused ultrasound for therapeutic applications.more » Learning Objectives: Develop a general understanding of the underlying technologies associated with optoacoustic / photoacoustic tomography and MRguided high-intensity focused ultrasound. Develop an understanding of the current methods of these new ultrasound-based technologies in preclinical research and clinical applications.« less

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

PubMed Central

Cao, Yang; Chen, Yuli; Yu, Tao; Guo, Yuan; Liu, Fengqiu; Yao, Yuanzhi; Li, Pan; Wang, Dong; Wang, Zhigang; Chen, Yu; Ran, Haitao

2018-01-01

Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release. PMID:29507623

SNR enhancement for catheter based intravascular photoacoustic/ultrasound imaging

NASA Astrophysics Data System (ADS)

Cho, Seonghee; Choi, Changhoon; Ahn, Joongho; Kim, Taehoon; Park, Sungjo; Park, Hyoeun; Kim, Jinmoo; Lee, Seunghoon; Kang, Yeonsu; Chang, Kiyuk; Kim, Yongmin; Kim, Chulhong

2017-03-01

Atherosclerosis, the most common cause of death, kills suddenly by arterial occlusion by thrombosis, which is caused by plaque rupture. Because a growing necrotic core is highly related to plaque rupture in atherosclerosis, distinguishing between fibrous plaque and lipid-rich plaque in real time is important, but has been challenging. Real-time photoacoustic imaging requires a pulse laser with high repetition rate, which tends to sacrifice pulse energy. Furthermore, a high repetition rate is hard to achieve at lipid-sensitive wavelengths, such as 1210 nm and 1720 nm. To address the unmet need, we have developed the algorithm for PA imaging. We successfully acquired ex vivo PA images from the lipid cores of arterial plaques in rabbit arteries, using a low-power 1064-nm laser. PA images were acquired with a custom-made catheter employing a single-element 40-MHz ultrasound transducer and a compact 1064-nm laser with the pulse energy of 5 μJ and the repetition rate of 24 kHz. Acquired raw data were processed in the time and frequency domains. In the time domain, a delay-and-sum algorithm was used for image enhancement. In the frequency domain, signals exceeding the MTF were removed. As a result, SNR was increased by about 10 dB without degrading spatial resolution. We were able to achieve high-speed and high-SNR lipid target imaging in animals in spite of the low lipid sensitivity of a 1064nm laser. These results show good promise for detecting lipid-rich plaques with a compact high-speed laser, which can be easily adapted for target clinical applications.

Musculoskeletal ultrasound in rheumatology in Korea: targeted ultrasound initiative survey.

PubMed

Kang, Taeyoung; Wakefield, Richard J; Emery, Paul

2016-04-01

In collaboration with the Targeted Ultrasound Initiative (TUI), to conduct the first study in Korea to investigate current practices in ultrasound use among Korean rheumatologists. We translated the TUI Global Survey into Korean and added questions to better understand the specific challenges facing rheumatologists in Korea. To target as many rheumatologists in Korea as possible, we created an on-line version of this survey, which was conducted from March to April 2013. Rheumatologists are in charge of ultrasound in many Korean hospitals. Rheumatologists in hospitals and private clinics use ultrasound to examine between one and five patients daily; they use ultrasound for diagnosis more than monitoring and receive compensation of about US$30-50 per patient. There are marked differences in the rates of ultrasound usage between rheumatologists who work in private practice compared with tertiary hospitals. Korean rheumatologists not currently using ultrasound in their practice appear eager to do so. This survey provides important insights into the current status of ultrasound in rheumatology in Korea and highlights several priorities; specifically, greater provision of formal training, standardization of reporting and accrual of greater experience among ultrasound users. If these needs are addressed, all rheumatology departments in Korea are likely to use ultrasound or have access to it in the future. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.

PubMed

Liu, Jian; Gao, Yun-Hua; Li, Ding-Dong; Gao, Yan-Chun; Hou, Ling-Mi; Xie, Ting

2014-01-01

To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (P<0.05). The ability of CEUS qualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

Double-scattering/reflection in a Single Nanoparticle for Intensified Ultrasound Imaging

PubMed Central

Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

2015-01-01

Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled). PMID:25739832

Ultrasound in gas-liquid systems: effects on solubility and mass transfer.

PubMed

Laugier, F; Andriantsiferana, C; Wilhelm, A M; Delmas, H

2008-09-01

The effect of ultrasound on the pseudo-solubility of nitrogen in water and on gas-liquid mass transfer kinetics has been investigated in an autoclave reactor equipped with a gas induced impeller. In order to use organic liquids and to investigate the effect of pressure, gas-liquid mass transfer coefficient was calculated from the evolution of autoclave pressure during gas absorption to avoid any side-effects of ultrasound on the concentrations measurements. Ultrasound effect on the apparent solubility is very low (below 12%). Conversely ultrasound greatly improves gas-liquid mass transfer, especially below gas induction speed, this improvement being boosted by pressure. In typical conditions of organic synthesis: 323 K, 1100 rpm, 10 bar, k(L).a is multiplied by 11 with ultrasound (20 kHz/62.6 W). The impact of sonication is much higher on gassing out than on gassing in. In the same conditions, this enhancement is at least five times higher for degassing.

Double-scattering/reflection in a single nanoparticle for intensified ultrasound imaging.

PubMed

Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

2015-03-05

Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled).

Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration with low-frequency, low-intensity (20 kHz, 100 mW/cm(2)) ultrasound exposure on carrageenan-induced arthritis in a mouse model.

PubMed

Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R; Touitou, Elka; Lerman, Melissa A; Lazarovici, Philip; Lewin, Peter A

2015-09-01

The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system

PubMed Central

Winter, Philipp; Müller-Werkmeister, Hendrik; Strand, Susanne; König, Jochem; Kempski, Oliver; Ringel, Florian; Kantelhardt, Sven R.; Keric, Naureen

2017-01-01

Background Catheter-based lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy for spontaneous intracerebral hemorrhage (ICH). The effectiveness of this therapy can be increased with ultrasound, but the optimal conditions are not yet clearly established. Using a novel in vitro system of blood clots previously developed by our group, we investigated various parameters of intralesional sonothrombolysis using an endosonography catheter in combination with rtPA. Methods Standardized human blood clots were equipped with a drainage catheter and weighed before and after 4 treatments: control (drainage only), rtPA only, ultrasound only and the combination of rtPA+ultrasound. The effectiveness of ultrasound was further analysed in terms of optimal frequency, duration and distance to the probe. Temperature and acoustic peak rarefaction pressure (APRP) were assessed to analyse potential adverse effects and quantify lysis. Histo-morphological analysis of the treated clots was performed by H&E staining and confocal laser scanning microscopy using fluorescent fibrinogen. Results The combined treatment rtPA+ultrasound achieved the highest lysis rates with a relative weight of 30.3%±5.5% (p≤0.0001) compared to all other groups. Similar results were observed when treating aged clots. Confocal fluorescent microscopy of the treated clots revealed a rarefied fibrin mesh without cavitations. No relevant temperature increase occurred (0.53±0.75°C). The optimal insonation treatment time was 1 hour. APRP measurements showed a lysis threshold of 515.5±113.4 kPa. Application of 10 MHz achieved optimal lysis and lysis radius, while simultaneously proving to be the best frequency for morphologic imaging of the clot and surrounding tissue. Conclusions These promising data provide the basis for an individualized minimal invasive ICH therapy by rtPA and sonothrombolysis independent of ICH age. PMID:29145482

Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.

PubMed

Stride, E P; Coussios, C C

2010-01-01

Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.

Contrast imaging in mouse embryos using high-frequency ultrasound.

PubMed

Denbeigh, Janet M; Nixon, Brian A; Puri, Mira C; Foster, F Stuart

2015-03-04

Ultrasound contrast-enhanced imaging can convey essential quantitative information regarding tissue vascularity and perfusion and, in targeted applications, facilitate the detection and measure of vascular biomarkers at the molecular level. Within the mouse embryo, this noninvasive technique may be used to uncover basic mechanisms underlying vascular development in the early mouse circulatory system and in genetic models of cardiovascular disease. The mouse embryo also presents as an excellent model for studying the adhesion of microbubbles to angiogenic targets (including vascular endothelial growth factor receptor 2 (VEGFR2) or αvβ3) and for assessing the quantitative nature of molecular ultrasound. We therefore developed a method to introduce ultrasound contrast agents into the vasculature of living, isolated embryos. This allows freedom in terms of injection control and positioning, reproducibility of the imaging plane without obstruction and motion, and simplified image analysis and quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine embryos were isolated from the uterus, gently exteriorized from the yolk sac and microbubble contrast agents were injected into veins accessible on the chorionic surface of the placental disc. Nonlinear contrast ultrasound imaging was then employed to collect a number of basic perfusion parameters (peak enhancement, wash-in rate and time to peak) and quantify targeted microbubble binding in an endoglin mouse model. We show the successful circulation of microbubbles within living embryos and the utility of this approach in characterizing embryonic vasculature and microbubble behavior.

Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and computed tomography (CT)--preliminary results.

PubMed

Wobser, Hella; Wiest, Reiner; Salzberger, Bernd; Wohlgemuth, Walter Alexander; Stroszczynski, Christian; Jung, Ernst-Michael

2014-01-01

To evaluate treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with a new real-time imaging fusion technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection computed tomography (CT) in comparison to conventional post-interventional follow-up. 40 patients with HCC (26 male, ages 46-81 years) were evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was regarded as "successful" treatment, whereas reduction to levels >25% was considered as "partial" treatment response. Homogenous lipiodol retention was regarded as successful treatment in non-enhanced CT. Post-interventional image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients (24/40), post-interventional image fusion with CEUS revealed residual tumor vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24 patients. In 16 patients (16/40), post-interventional image fusion with CEUS demonstrated successful treatment, but follow-up CT detected residual viable tumor (6/16). Non-enhanced CT did not identify any case of treatment failure. Image fusion with CEUS assessed treatment efficacy with a specificity of 100%, sensitivity of 80% and a positive predictive value of 1 (negative predictive value 0.63). Image fusion of CEUS with CT allows a reliable, highly specific post-interventional evaluation of embolization response with good sensitivity without any further radiation exposure. It can detect residual viable tumor at early state, resulting in a close patient monitoring or re-therapy.

Integrated medical school ultrasound: development of an ultrasound vertical curriculum.

PubMed

Bahner, David P; Adkins, Eric J; Hughes, Daralee; Barrie, Michael; Boulger, Creagh T; Royall, Nelson A

2013-07-02

Physician-performed focused ultrasonography is a rapidly growing field with numerous clinical applications. Focused ultrasound is a clinically useful tool with relevant applications across most specialties. Ultrasound technology has outpaced the education, necessitating an early introduction to the technology within the medical education system. There are many challenges to integrating ultrasound into medical education including identifying appropriately trained faculty, access to adequate resources, and appropriate integration into existing medical education curricula. As focused ultrasonography increasingly penetrates academic and community practices, access to ultrasound equipment and trained faculty is improving. However, there has remained the major challenge of determining at which level is integrating ultrasound training within the medical training paradigm most appropriate. The Ohio State University College of Medicine has developed a novel vertical curriculum for focused ultrasonography which is concordant with the 4-year medical school curriculum. Given current evidenced-based practices, a curriculum was developed which provides medical students an exposure in focused ultrasonography. The curriculum utilizes focused ultrasonography as a teaching aid for students to gain a more thorough understanding of basic and clinical science within the medical school curriculum. The objectives of the course are to develop student understanding in indications for use, acquisition of images, interpretation of an ultrasound examination, and appropriate decision-making of ultrasound findings. Preliminary data indicate that a vertical ultrasound curriculum is a feasible and effective means of teaching focused ultrasonography. The foreseeable limitations include faculty skill level and training, initial cost of equipment, and incorporating additional information into an already saturated medical school curriculum. Focused ultrasonography is an evolving concept in medicine

Ultrasound assisted biogas production from landfill leachate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oz, Nilgün Ayman, E-mail: nilgunayman@comu.edu.tr; Yarimtepe, Canan Can

Highlights: • Effect of low frequency ultrasound pretreatment on leachate was investigated. • Three different ultrasound energy inputs (200, 400 and 600 W/l) was applied. • Low-frequency ultrasound treatment increased soluble COD in landfill leachate. • Application of ultrasound to leachate increased biogas production about 40%. • Application of ultrasound to leachate increased total methane production rate about 20%. - Abstract: The aim of this study is to increase biogas production and methane yield from landfill leachate in anaerobic batch reactors by using low frequency ultrasound as a pretreatment step. In the first part of the study, optimum conditions formore » solubilization of organic matter in leachate samples were investigated using various sonication durations at an ultrasound frequency of 20 kHz. The level of organic matter solubilization during ultrasonic pretreatment experiments was determined by calculating the ratio of soluble chemical oxygen demand (sCOD) to total chemical oxygen demand (tCOD). The sCOD/tCOD ratio was increased from 47% in raw leachate to 63% after 45 min sonication at 600 W/l. Non-parametric Friedman’s test indicated that ultrasonic pretreatment has a significant effect on sCOD parameter for leachate (p < 0.05). In the second part of the study, anaerobic batch reactors were operated for both ultrasonically pretreated and untreated landfill leachate samples in order to assess the effect of sonication on biogas and methane production rate. In anaerobic batch reactor feed with ultrasonically pretreated leachate, 40% more biogas was obtained compared to the control reactor. For statistical analysis, Mann–Whitney U test was performed to compare biogas and methane production rates for raw and pretreated leachate samples and it has been found that ultrasonic pretreatment significantly enhanced biogas and methane production rates from leachate (p < 0.05) in anaerobic batch reactors. The overall results showed that low

Simulating the multi-disciplinary care team approach: Enhancing student understanding of anatomy through an ultrasound-anchored interprofessional session.

PubMed

Luetmer, Marianne T; Cloud, Beth A; Youdas, James W; Pawlina, Wojciech; Lachman, Nirusha

2018-01-01

Quality of healthcare delivery is dependent on collaboration between professional disciplines. Integrating opportunities for interprofessional learning in health science education programs prepares future clinicians to function as effective members of a multi-disciplinary care team. This study aimed to create a modified team-based learning (TBL) environment utilizing ultrasound technology during an interprofessional learning activity to enhance musculoskeletal anatomy knowledge of first year medical (MD) and physical therapy (PT) students. An ultrasound demonstration of structures of the upper limb was incorporated into the gross anatomy courses for first-year MD (n = 53) and PT (n = 28) students. Immediately before the learning experience, all students took an individual readiness assurance test (iRAT) based on clinical concepts regarding the assigned study material. Students observed while a physical medicine and rehabilitation physician demonstrated the use of ultrasound as a diagnostic and procedural tool for the shoulder and elbow. Following the demonstration, students worked within interprofessional teams (n = 14 teams, 5-6 students per team) to review the related anatomy on dissected specimens. At the end of the session, students worked within interprofessional teams to complete a collaborative clinical case-based multiple choice post-test. Team scores were compared to the mean individual score within each team with the Wilcoxon signed-rank test. Students scored higher on the collaborative post-test (95.2 ±10.2%) than on the iRAT (66.1 ± 13.9% for MD students and 76.2 ±14.2% for PT students, P < 0.0001). Results suggest that this interprofessional team activity facilitated an improved understanding and clinical application of anatomy. Anat Sci Educ 11: 94-99. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

NASA Astrophysics Data System (ADS)

Chiriacò, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto; Ragusa, Andrea; Sbenaglia, Enzo Antonio; Dipaola, Lucia; Casciaro, Sergio

2013-07-01

Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

Development of a Cancer Treatment with the Concomitant Use of Low-Intensity Ultrasound: Entering the Age of Simultaneous Diagnosis and Treatment

PubMed Central

Emoto, Makoto

2014-01-01

In recent years, studies using ultrasound energy for cancer treatment have advanced, thus revealing the enhancement of drug effects by employing low-intensity ultrasound. Furthermore, anti-angiogenesis against tumors is now attracting attention as a new cancer treatment. Therefore, we focused on the biological effects and the enhancement of drug effects brought by this low-intensity ultrasound energy and reported on the efficacy against a uterine sarcoma model, by implementing the basic studies, for the first time, including the concomitant use of low-intensity ultrasound irradiation, as an expected new antiangiogenic therapy for cancer treatment. Furthermore, we have succeeded in simultaneously utilizing low-intensity ultrasound in both diagnosis and treatment, upon real time evaluation of the anti-tumor effects and anti-angiogenesis effects using color Doppler ultrasound imaging. Although the biological effects of ultrasound have not yet been completely clarified, transient stomas were formed (Sonoporation) in cancer cells irradiated by low-intensity ultrasound and it is believed that the penetration effect of drugs is enhanced due to the drug being more charged inside the cell through these stomas. Furthermore, it has become clear that the concomitant therapy of anti-angiogenesis drugs and low-intensity ultrasound blocks the angiogenic factor VEGF produced by cancer cells, inhibits the induction of circulating endothelial progenitor cells in the bone marrow, and expedites angiogenic inhibitor TSP-1. Based on research achievements in recent years, we predict that the current diagnostic device for color Doppler ultrasound imaging will be improved in the near future, bringing with it the arrival of an age of “low-intensity ultrasound treatment that simultaneously enables diagnosis and treatment of cancer in real time.” PMID:26852677

Ultrasound influence on the activation step before electroless coating.

PubMed

Touyeras, F; Hihn, J Y; Delalande, S; Viennet, R; Doche, M L

2003-10-01

This paper is devoted to the electroless plating of non-conductive substrates under ultrasound at 530 kHz. The ultrasonic irradiation is applied to the activation and to the plating steps. Effects are measured by following the final copper thickness obtained in 1 h of plating time, easily correlated to the average plating rate. It appears that ultrasound has a strong influence on the plating rates enhancement, and assumptions can be made that this increase could be linked to the catalyst cleaning. This is confirmed by XPS measurements.

Enhancement of convective drying by application of airborne ultrasound - a response surface approach.

PubMed

Beck, Svenja M; Sabarez, Henry; Gaukel, Volker; Knoerzer, Kai

2014-11-01

Drying is one of the oldest and most commonly used processes in the food manufacturing industry. The conventional way of drying is by forced convection at elevated temperatures. However, this process step often requires a very long treatment time, is highly energy consuming and detrimental to the product quality. Therefore, an investigation of whether the drying time and temperature can be reduced with the assistance of an airborne ultrasound intervention is of interest. Previous studies have shown that contact ultrasound can accelerate the drying process. It is assumed that mechanical vibrations, creating micro channels in the food matrix or keeping these channels from collapsing upon drying, are responsible for the faster water removal. In food samples, due to their natural origin, drying is also influenced by fluctuations in tissue structure, varying between different trials. For this reason, a model food system with thermo-physical properties and composition (water, cellulose, starch, fructose) similar to those of plant-based foods has been used in this study. The main objective was, therefore, to investigate the influence of airborne ultrasound conditions on the drying behaviour of the model food. The impact of airborne ultrasound at various power levels, drying temperature, relative humidity of the drying air, and the air speed was analysed. To examine possible interactions between these parameters, the experiments were designed with a Response Surface Method using Minitab 16 Statistical Software (Minitab Inc., State College, PA, USA). In addition, a first attempt at improving the process conditions and performance for better suitability and applicability in industrial scale processing was undertaken by non-continuous/intermittent sonication. Copyright © 2014 Elsevier B.V. All rights reserved.

3-D transcranial ultrasound imaging with bilateral phase aberration correction of multiple isoplanatic patches: a pilot human study with microbubble contrast enhancement.

PubMed

Lindsey, Brooks D; Nicoletto, Heather A; Bennett, Ellen R; Laskowitz, Daniel T; Smith, Stephen W

2014-01-01

With stroke currently the second-leading cause of death globally, and 87% of all strokes classified as ischemic, the development of a fast, accessible, cost-effective approach for imaging occlusive stroke could have a significant impact on health care outcomes and costs. Although clinical examination and standard computed tomography alone do not provide adequate information for understanding the complex temporal events that occur during an ischemic stroke, ultrasound imaging is well suited to the task of examining blood flow dynamics in real time and may allow for localization of a clot. A prototype bilateral 3-D ultrasound imaging system using two matrix array probes on either side of the head allows for correction of skull-induced aberration throughout two entire phased array imaging volumes. We investigated the feasibility of applying this custom correction technique in five healthy volunteers with Definity microbubble contrast enhancement. Subjects were scanned simultaneously via both temporal acoustic windows in 3-D color flow mode. The number of color flow voxels above a common threshold increased as a result of aberration correction in five of five subjects, with a mean increase of 33.9%. The percentage of large arteries visualized by 3-D color Doppler imaging increased from 46% without aberration correction to 60% with aberration correction. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Investigation of microbubble response to long pulses used in ultrasound-enhanced drug delivery.

PubMed

Mannaris, Christophoros; Averkiou, Michalakis A

2012-04-01

In current drug delivery approaches, microbubbles and drugs can be co-administered while ultrasound is applied. The mechanism of microbubble interaction with ultrasound, the drug and the cells is not fully understood. The aim of this study was to investigate microbubble response to long ultrasonic pulses used in drug delivery approaches. Two different in vitro set-ups were considered: with the microbubbles diluted in an enclosure and with the microbubbles flowing in a capillary tube. Acoustic streaming, which influences the observed bubble response, was observed in "typical" drug delivery conditions in the first set-up. With the capillary set-up, streaming effects were avoided and accurate bubble responses were recorded. The diffraction pattern of the source greatly influences the bubble response and in different locations of the field different bubble responses are observed. At low nondestructive pressures, microbubbles can oscillate for thousands of cycles repeatedly. At high acoustic pressures (at 1 MHz), most bubble activity disappeared within about 100 μs despite the length of the pulse, mainly due to violent bubble destruction and subsequent accelerated diffusion. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Focused ultrasound guided relocation of kidney stones.

PubMed

Abrol, Nitin; Kekre, Nitin S

2015-01-01

Complete removal of all fragments is the goal of any intervention for urinary stones. This is more important in lower pole stones where gravity and spatial orientation of lower pole infundibulum may hinder spontaneous passage of fragments. Various adjuvant therapies (inversion, diuresis, percussion, oral citrate, etc.) are described to enhance stone-free rate but are not widely accepted. Focused ultrasound-guided relocation of fragments is a recently described technique aimed at improving results of intervention for stone disease. Purpose of this review is to discuss development of this technology and its potential clinical applications. Pubmed search was made using key words "Focused ultrasound" and "kidney stone". All English language articles were reviewed by title. Relevant studies describing development and application of focused ultrasound in renal stones were selected for review. Focused ultrasound has proven its efficacy in successfully relocating up to 8 mm stone fragments in vitro and in pigs. Relocation is independent of stone composition. The latest model allows imaging and therapy with a single handheld probe facilitating its use by single operator. The acoustic energy delivered by the new prototype is even less than that used for extracorporeal shock wave lithotripsy. Therapeutic exposure has not caused thermal injury in pig kidneys. Focused ultrasound-guided relocation of stones is feasible. Though it is safe in application in pigs, technology is awaiting approval for clinical testing in human beings. This technology has many potential clinical applications in the management of stone disease.

Characteristics of pectinase treated with ultrasound both during and after the immobilization process.

PubMed

Ma, Xiaobin; Wang, Danli; Yin, Michelle; Lucente, Juliet; Wang, Wenjun; Ding, Tian; Ye, Xingqian; Liu, Donghong

2017-05-01

In this study, ultrasound was applied both during and after the immobilization process and characteristics of different immobilized pectinase samples were studied. When introduced during the immobilization process, ultrasound at an intensity of 9WmL -1 for 20min increased the immobilization yield 92.28% more than the control. When introduced to the already immobilized pectinase, ultrasound at an intensity of 4.5WmL -1 for 10min increased the pectinase activity by 30.05%. Results of scanning electron microscope demonstrated that ultrasound increased surface area and loosened structures of immobilized enzymes. Higher V max and lower K m were obtained after ultrasound treatment, indicating the increased catalytic efficiency and enhanced affinity of immobilized pectinase. Furthermore, the optimum temperature and pH for free and immobilized pectinase remained unchanged at 50°C and pH 4. Thermostability, reaction stability and reusability of two ultrasound-treated pectinase enzymes slightly decreased due to structural matrix changes. Copyright © 2016 Elsevier B.V. All rights reserved.

Sonochemiluminescence observation of lipid- and polymer-shelled ultrasound contrast agents in 1.2 MHz focused ultrasound field.

PubMed

Qiao, Yangzi; Cao, Hua; Zhang, Shusheng; Yin, Hui; Wan, Mingxi

2013-01-01

Ultrasound contrast agents (UCAs) are frequently added into the focused ultrasound field as cavitation nuclei to enhance the therapeutic efficiency. Since their presence will distort the pressure field and make the process unpredictable, comprehension of their behaviors especially the active zone spatial distribution is an important part of better monitoring and using of UCAs. As shell materials can strongly alter the acoustic behavior of UCAs, two different shells coated UCAs, lipid-shelled and polymer-shelled UCAs, in a 1.2 MHz focused ultrasound field were studied by the Sonochemiluminescence (SCL) method and compared. The SCL spatial distribution of lipid-shelled group differed from that of polymer-shelled group. The shell material and the character of focused ultrasound field work together to the SCL distribution, causing the lipid-shelled group to have a maximum SCL intensity in pre-focal region at lower input power than that of polymer-shelled group, and a brighter SCL intensity in post-focal region at high input power. The SCL inactive area of these two groups both increased with the input power. The general behavior of the UCAs can be studied by both the average SCL intensity and the backscatter signals. As polymer-shelled UCAs are more resistant to acoustic pressure, they had a higher destruction power and showed less reactivation than lipid-shelled ones. Copyright © 2012 Elsevier B.V. All rights reserved.

Ultrasound in Arthritis.

PubMed

Sudoł-Szopińska, Iwona; Schueller-Weidekamm, Claudia; Plagou, Athena; Teh, James

2017-09-01

Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

The Sound Games: Introducing Gamification into Stanford's Orientation on Emergency Ultrasound.

PubMed

Lobo, Viveta; Stromberg, Andrew Q; Rosston, Peter

2017-09-18

Point-of-care ultrasound is a critical component of graduate medical training in emergency medicine. Innovation in ultrasound teaching methods is greatly needed to keep up with a changing medical landscape. A field-wide trend promoting simulation and technology-enhanced learning is underway in an effort to improve patient care, as well as patient safety. In an effort to both motivate students and increase their skill retention, training methods are shifting towards a friendly competition model and are gaining popularity nationwide. In line with this emerging trend, Stanford incorporated the Sound Games - an educational ultrasound event with a distinctly competitive thread - within its existing two-day point-of-care ultrasound orientation course for emergency medicine interns. In this study, we demonstrate successful implementation of the orientation program, significant learning gains in participants, and overall student satisfaction with the course.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

PubMed

Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

2014-12-01

Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it

Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An In Vitro and In Vivo Comparison Study.

PubMed

Hyvelin, Jean-Marc; Gaud, Emmanuel; Costa, Maria; Helbert, Alexandre; Bussat, Philippe; Bettinger, Thierry; Frinking, Peter

2017-05-01

To compare physicochemical characteristics and in vitro and in vivo contrast-enhanced ultrasound imaging performance of 3 commercially available ultrasound contrast agents: SonoVue (Bracco Imaging SpA, Colleretto Giacosa, Italy; also marketed as Lumason in the USA), Definity (Lantheus Medical Imaging, North Billerica, MA) and Optison (GE Healthcare AS, Oslo, Norway). Physicochemical characteristics were measured with a Multisizer Coulter Counter (Beckman Coulter, Fullerton, CA). Two ultrasound systems (Aplio 500; Toshiba Medical Systems Corp, Tochigi-ken, Japan; and Logiq E9; GE Healthcare, Little Chalfont, England) were used with different transducers. Contrast enhancement was measured in vitro by dose-ranging measurements using a custom-built beaker setup; in vivo imaging performances were compared in pigs (heart and liver) and rabbits (liver). Quantitative analyses were performed with VueBox quantification software (Bracco Suisse SA, Plan-les-Ouates, Switzerland). Measured physicochemical characteristics were in agreement with those provided by the manufacturers. In vitro data demonstrated that the performance of SonoVue was similar to or better than that of Definity but superior to Optison (normalized scattered power 2- to 10-fold higher with SonoVue). Similar results were obtained in vivo, although the duration of enhancement in the pig heart was longer for SonoVue compared to Definity, and quantitative analysis revealed higher enhancement for SonoVue (1.5-fold increase). For liver imaging, SonoVue and Definity showed similar contrast enhancement and duration of enhancement, but compared to Optison, both peak enhancement and duration of enhancement were superior for SonoVue (up to 2-fold increase). Imaging performance of SonoVue was similar to or slightly better than that of Definity, but it was superior to Optison for the conditions used in this study. © 2017 by the American Institute of Ultrasound in Medicine.

Ultrasound in Enzyme Activation and Inactivation

NASA Astrophysics Data System (ADS)

Mawson, Raymond; Gamage, Mala; Terefe, Netsanet Shiferaw; Knoerzer, Kai

As discussed in previous chapters, most effects due to ultrasound arise from cavitation events, in particular, collapsing cavitation bubbles. These collapsing bubbles generate very high localized temperatures and pressure shockwaves along with micro-streaming that is associated with high shear forces. These effects can be used to accelerate the transport of substrates and reaction products to and from enzymes, and to enhance mass transfer in enzyme reactor systems, and thus improve efficiency. However, the high velocity streaming, together with the formation of hydroxy radicals and heat generation during collapsing of bubbles, may also potentially affect the biocatalyst stability, and this can be a limiting factor in combined ultrasound/enzymatic applications. Typically, enzymes can be readily denatured by slight changes in environmental conditions, including temperature, pressure, shear stress, pH and ionic strength.

Guiding tissue regeneration with ultrasound in vitro and in vivo

NASA Astrophysics Data System (ADS)

Dalecki, Diane; Comeau, Eric S.; Raeman, Carol H.; Child, Sally Z.; Hobbs, Laura; Hocking, Denise C.

2015-05-01

Developing new technologies that enable the repair or replacement of injured or diseased tissues is a major focus of regenerative medicine. This paper will discuss three ultrasound technologies under development in our laboratories to guide tissue regeneration both in vitro and in vivo. A critical obstacle in tissue engineering is the need for rapid and effective tissue vascularization strategies. To address this challenge, we are developing acoustic patterning techniques for microvascular tissue engineering. Acoustic radiation forces associated with ultrasound standing wave fields provide a rapid, non-invasive approach to spatially pattern cells in three dimensions without affecting cell viability. Acoustic patterning of endothelial cells leads to the rapid formation of microvascular networks throughout the volumes of three-dimensional hydrogels, and the morphology of the resultant microvessel networks can be controlled by design of the ultrasound field. A second technology under development uses ultrasound to noninvasively control the microstructure of collagen fibers within engineered tissues. The microstructure of extracellular matrix proteins provides signals that direct cell functions critical to tissue regeneration. Thus, controlling collagen microfiber structure with ultrasound provides a noninvasive approach to regulate the mechanical properties of biomaterials and control cellular responses. The third technology employs therapeutic ultrasound to enhance the healing of chronic wounds. Recent studies demonstrate increased granulation tissue thickness and collagen deposition in murine dermal wounds exposed to pulsed ultrasound. In summary, ultrasound technologies offer noninvasive approaches to control cell behaviors and extracellular matrix organization and thus hold great promise to advance tissue regeneration in vitro and in vivo.

Ultrasound imaging beyond the vasculature with new generation contrast agents.

PubMed

Perera, Reshani H; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan; Exner, Agata A

2015-01-01

Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. © 2015 Wiley Periodicals, Inc.

Ultrasound Imaging Beyond the Vasculature with New Generation Contrast Agents

PubMed Central

Perera, Reshani H.; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan

2015-01-01

Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 μm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. PMID:25580914

Nonrigid motion compensation in B-mode and contrast enhanced ultrasound image sequences of the carotid artery

NASA Astrophysics Data System (ADS)

Carvalho, Diego D. B.; Akkus, Zeynettin; Bosch, Johan G.; van den Oord, Stijn C. H.; Niessen, Wiro J.; Klein, Stefan

2014-03-01

In this work, we investigate nonrigid motion compensation in simultaneously acquired (side-by-side) B-mode ultrasound (BMUS) and contrast enhanced ultrasound (CEUS) image sequences of the carotid artery. These images are acquired to study the presence of intraplaque neovascularization (IPN), which is a marker of plaque vulnerability. IPN quantification is visualized by performing the maximum intensity projection (MIP) on the CEUS image sequence over time. As carotid images contain considerable motion, accurate global nonrigid motion compensation (GNMC) is required prior to the MIP. Moreover, we demonstrate that an improved lumen and plaque differentiation can be obtained by averaging the motion compensated BMUS images over time. We propose to use a previously published 2D+t nonrigid registration method, which is based on minimization of pixel intensity variance over time, using a spatially and temporally smooth B-spline deformation model. The validation compares displacements of plaque points with manual trackings by 3 experts in 11 carotids. The average (+/- standard deviation) root mean square error (RMSE) was 99+/-74μm for longitudinal and 47+/-18μm for radial displacements. These results were comparable with the interobserver variability, and with results of a local rigid registration technique based on speckle tracking, which estimates motion in a single point, whereas our approach applies motion compensation to the entire image. In conclusion, we evaluated that the GNMC technique produces reliable results. Since this technique tracks global deformations, it can aid in the quantification of IPN and the delineation of lumen and plaque contours.

A collimated focused ultrasound beam of high acoustic transmission and minimum diffraction achieved by using a lens with subwavelength structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Zhou; Tu, Juan; Cheng, Jianchun

An acoustic focusing lens incorporated with periodically aligned subwavelength grooves corrugated on its spherical surface has been developed. It is demonstrated theoretically and experimentally that acoustic focusing achieved by using the lens can suppress the relative side-lobe amplitudes, enhance the focal gain, and minimize the shifting of the focus. Use of the lens coupled with a planar ultrasound transducer can generate an ultrasound beam with enhanced acoustic transmission and collimation effect, which offers the capability of improving the safety, efficiency, and accuracy of targeted surgery implemented by high intensity focused ultrasound.

Diagnosis of sub-centimetre breast lesions: combining BI-RADS-US with strain elastography and contrast-enhanced ultrasound-a preliminary study in China.

PubMed

Xiao, Xiaoyun; Jiang, Qiongchao; Wu, Huan; Guan, Xiaofeng; Qin, Wei; Luo, Baoming

2017-06-01

To compare the diagnostic efficacies of B-mode ultrasound (US), strain elastography (SE), contrast-enhanced ultrasound (CEUS) and the combination of these modalities for breast lesions <1 cm in size. Between January 2013 and October 2015, 203 inpatients with 209 sub-centimetre breast lesions categorised as BI-RADS-US (Breast Imaging Reporting and Data System for Ultrasound) 3-5 were included. US, SE and CEUS were performed to evaluate each lesion. The diagnostic performances of different ultrasonic modalities were compared. The diagnostic efficacies of BI-RADS-US and our re-rating systems were also compared. The pathology findings were used as the reference standard. The specificities of US, SE and CEUS for tumour differentiation were 17.4 %, 56.2 % and 86.0 %, respectively (P < 0.05); and the sensitivities were 100 %, 93.2 % and 93.2 % for US, SE and CEUS, respectively (P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.867 for original BI-RADS-US, 0.882 for BI-RADS-US combined with only SE, 0.953 for BI-RADS-US combined with only CEUS and 0.924 for BI-RADS-US combined with both SE and CEUS. The best combination was BI-RADS-US combined with only CEUS. Evaluating sub-centimetre breast lesions with SE and CEUS could increase the diagnostic specificity while retaining high sensitivity compared with B-mode ultrasound. • Evaluating breast lesions with SE and CEUS could increase the diagnostic specificity • SE and CEUS offer alternatives to biopsy and possibly allow shorter-interval follow-ups • BI-RADS-US combined with CEUS exhibited the best diagnostic performance.

Numerical investigation of the inertial cavitation threshold under multi-frequency ultrasound.

PubMed

Suo, Dingjie; Govind, Bala; Zhang, Shengqi; Jing, Yun

2018-03-01

Through the introduction of multi-frequency sonication in High Intensity Focused Ultrasound (HIFU), enhancement of efficiency has been noted in several applications including thrombolysis, tissue ablation, sonochemistry, and sonoluminescence. One key experimental observation is that multi-frequency ultrasound can help lower the inertial cavitation threshold, thereby improving the power efficiency. However, this has not been well corroborated by the theory. In this paper, a numerical investigation on the inertial cavitation threshold of microbubbles (MBs) under multi-frequency ultrasound irradiation is conducted. The relationships between the cavitation threshold and MB size at various frequencies and in different media are investigated. The results of single-, dual and triple frequency sonication show reduced inertial cavitation thresholds by introducing additional frequencies which is consistent with previous experimental work. In addition, no significant difference is observed between dual frequency sonication with various frequency differences. This study, not only reaffirms the benefit of using multi-frequency ultrasound for various applications, but also provides a possible route for optimizing ultrasound excitations for initiating inertial cavitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Gold-nanorod contrast-enhanced photoacoustic micro-imaging of focused-ultrasound induced blood-brain-barrier opening in a rat model

NASA Astrophysics Data System (ADS)

Wang, Po-Hsun; Liu, Hao-Li; Hsu, Po-Hung; Lin, Chia-Yu; Chris Wang, Churng-Ren; Chen, Pin-Yuan; Wei, Kuo-Chen; Yen, Tzu-Chen; Li, Meng-Lin

2012-06-01

In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ~800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

PubMed

Mano, Yui; Saito, Ryuta; Haga, Yoichi; Matsunaga, Tadao; Zhang, Rong; Chonan, Masashi; Haryu, Shinya; Shoji, Takuhiro; Sato, Aya; Sonoda, Yukihiko; Tsuruoka, Noriko; Nishiyachi, Keisuke; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Tominaga, Teiji

2016-05-01

OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 μl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way

Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology.

PubMed

Roberts, V H J; Morgan, T K; Bednarek, P; Morita, M; Burton, G J; Lo, J O; Frias, A E

2017-12-01

Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy? Microvascular filling of the IVS was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed. During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester. Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries. Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis. Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was

Degradation of Acid Blue 25 in aqueous media using 1700kHz ultrasonic irradiation: ultrasound/Fe(II) and ultrasound/H(2)O(2) combinations.

PubMed

Ghodbane, Houria; Hamdaoui, Oualid

2009-06-01

In this work, the sonolytic degradation of an anthraquinonic dye, C.I. Acid Blue 25 (AB25), in aqueous phase using high frequency ultrasound waves (1700kHz) for an acoustic power of 14W was investigated. The sonochemical efficiency of the reactor was evaluated by potassium iodide dosimeter, Fricke reaction and hydrogen peroxide production yield. The three investigated methods clearly show the production of oxidizing species during sonication and well reflect the sonochemical effects of high frequency ultrasonic irradiation. The effect of operational conditions such as the initial AB25 concentration, solution temperature and pH on the degradation of AB25 was studied. Additionally, the influence of addition of salts on the degradation of dye was examined. The rate of AB25 degradation was dependent on initial dye concentration, pH and temperature. Addition of salts increased the degradation of dye. Experiments conducted using distilled and natural waters demonstrated that the degradation was more efficient in the natural water compared to distilled water. To increase the efficiency of AB25 degradation, experiments combining ultrasound with Fe(II) or H(2)O(2) were conducted. Fe(II) induced the dissociation of ultrasonically produced hydrogen peroxide, leading to additional OH radicals which enhance the degradation of dye. The combination of ultrasound with hydrogen peroxide looks to be a promising option to increase the generation of free radicals. The concentration of hydrogen peroxide plays a crucial role in deciding the extent of enhancement obtained for the combined process. The results of the present work indicate that ultrasound/H(2)O(2) and ultrasound/Fe(II) processes are efficient for the degradation of AB25 in aqueous solutions by high frequency ultrasonic irradiation.

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma.

PubMed

Pollard, R E; Fuller, M C; Steffey, M A

2017-06-01

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client-owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast-enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound. © 2015 John Wiley & Sons Ltd.

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

PubMed Central

Deshpande, Mangesh C.; Prausnitz, Mark R.

2007-01-01

Ultrasound and poly(ethylenimine) (PEI) have each separately been shown to increase DNA transfection efficiency. This study tested the hypothesis that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. This in vitro study assessed transfection efficiency of two different DNA plasmids encoding green fluorescent protein and firefly luciferase in two different cells types, a primary culture of human aortic smooth muscle cells and an immortal line of human prostrate cancer cells. We found that ultrasound sonication increased transfection up to 18-fold, DNA complexation with PEI increased transfection up to 90-fold, and the combination of ultrasound and PEI synergistically increased transfection up to 200-fold, which resulted in reporter gene expression by 34% of cells. Kinetic measurements found that the effects of ultrasound alone acted quickly, whereas increased transfection by PEI either alone or in combination with ultrasound strongly benefited from a 4-h incubation with the DNA plasmid after sonication. Although serum reduced absolute expression levels, it did not affect the relative increase in transfection when ultrasound was added to PEI enhancement. Flow cytometry measurements showed that sonication increased intracellular uptake of labelled DNA complexed to PEI by 55% relative to PEI complexation alone. Electrophoresis assay showed no damage to DNA or PEI-DNA complexes after sonication. Overall, these results suggest that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. PMID:17258835

Ultrasound-mediated oxygen delivery from chitosan nanobubbles.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Rolfo, Alessandro; Balbis, Sonia; Madonnaripa, Daniele; Caniggia, Isabella; Guiot, Caterina

2009-08-13

Ultrasound (US) energy combined with gas-filled microbubbles has been used for several years in medical imaging. This study investigated the ability of oxygen-loaded chitosan bubbles to exchange oxygen in the presence or in the absence of US. Oxygen delivery is enhanced by sonication and both frequency and time duration of US affected the exchange kinetics.

Influence of extrinsic operational parameters on salt diffusion during ultrasound assisted meat curing.

PubMed

Inguglia, Elena S; Zhang, Zhihang; Burgess, Catherine; Kerry, Joseph P; Tiwari, Brijesh K

2018-02-01

The present study investigated the effect of geometric parameters of the ultrasound instrument during meat salting in order to enhance salt diffusion and salt distribution in pork meat on a lab scale. The effects of probe size (∅2.5 and 1.3cm) and of different distances between the transducer and the meat sample (0.3, 0.5, and 0.8cm) on NaCl diffusion were investigated. Changes in the moisture content and NaCl gain were used to evaluate salt distribution and diffusion in the samples, parallel and perpendicular to ultrasound propagation direction. Results showed that 0.3cm was the most efficient distance between the probe and the sample to ensure a higher salt diffusion rate. A distance of 0.5cm was however considered as a trade-off distance to ensure salt diffusion and maintenance of meat quality parameters. The enhancement of salt diffusion by ultrasound was observed to decrease with increased horizontal distance from the probe. This study is of valuable importance for meat processing industries willing to apply new technologies on a larger scale and with defined operational standards. The data suggest that the geometric parameters of ultrasound systems can have strong influence on the efficiency of ultrasonic enhancement of NaCl uptake in meat and can be a crucial element in determining salt uptake during meat processing. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

PubMed

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Ultrasound contrast agents: an overview.

PubMed

Cosgrove, David

2006-12-01

With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI<0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

Differential diagnosis of gastric cancer and gastritis: the role of contrast-enhanced ultrasound (CEUS).

PubMed

Xue, Heng; Ge, Hui-Yu; Miao, Li-Ying; Wang, Shu-Min; Zhao, Bo; Wang, Jin-Rui; Cui, Li-Gang

2017-03-01

To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) (p < 0.001). Blurred, angular, or spiculated serosa margin and increased echogenicity in perigastric fat appeared only in cancer (10/58, 17.2%), and all of them proved to be pathologic T3 or T4 stage. On CEUS, gastric cancer usually manifested as diffused enhancement without comb-teeth-like vessels (parallel curvilinear structures representing arterial branching within the gastric wall) (56/58, 96.6%), while these vessels presented in most gastritis (19/24, 79.2%, p < 0.001). For quantitative analysis, the malignant lesions showed later and lower enhancement (p < 0.001), and they also had slower speed to reach the peak intensity (p < 0.001). On CEUS, the absence of comb-teeth-like vessel is most reliable for diagnosing malignancy, and the sensitivity, specificity, and accuracy were 96.5%, 79.2%, and 91.5%, respectively. Our results demonstrated the usefulness and accuracy of US and CEUS in differential diagnosis of gastric cancer and gastritis. CEUS has the potential to make the diagnosis more accurate.

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging.

PubMed

Wallace, N; Dicker, S; Lewin, P; Wrenn, S P

2014-12-01

This study aims to bridge the gap between transport mechanisms of an improved ultrasound contrast agent (UCA) and its resulting behavior in a clinical imaging study. Phospholipid-shelled microbubbles nested within the aqueous core of a polymer microcapsule are examined for their use and feasibility as an improved UCA. The nested formulation provides contrast comparable to traditional formulations, specifically an SF6 microbubble coated by a DSPC PEG-3000 monolayer, with the advantage that contrast persists at least nine times longer in a mock clinical, in vitro setting. The effectiveness of the sample was measured using a contrast ratio in units of decibels (dB) which compares the brightness of the nested microbubbles to a reference value of a phantom tissue mimic. During a 40min imaging study, six nesting formulations with average outer capsule diameters of 1.95, 2.53, 5.55, 9.95, 14.95, and 20.51μm reached final contrast ratio values of 0.25, 2.35, 3.68, 4.51, 5.93, and 8.00dB, respectively. The starting contrast ratio in each case was approximately 8dB and accounts for the brightness attributed to the nesting shell. As compared with empty microcapsules (no microbubbles nested within), enhancement of the initial contrast ratio increased systematically with decreasing microcapsule size. The time required to reach a steady state in the temporal contrast ratio profile also varied with microcapsule diameter and was found to be 420s for each of the four smallest shell diameters and 210s and 150s, respectively, for the largest two shell diameters. All nested formulations were longer-lived and gave higher final contrast ratios than a control sample comprising un-nested, but otherwise equivalent, microbubbles. Specifically, the contrast ratio of the un-nested microbubbles decreased to a negative value after 4min of continuous ultrasound exposure with complete disappearance of the microbubbles after 15min whereas all nested formulations maintained positive contrast ratio

Mesoporous silica nanoparticles engineered for ultrasound-induced uptake by cancer cells.

PubMed

Paris, Juan L; Manzano, Miguel; Cabañas, M Victoria; Vallet-Regí, María

2018-04-05

A novel smart hierarchical ultrasound-responsive mesoporous silica nanocarrier for cancer therapy is presented here. This dynamic nanosystem has been designed to display different surface characteristics during its journey towards tumor cells. Initially, the anticancer-loaded nanocarriers are shielded with a polyethylene glycol layer. Upon exposure to high frequency ultrasound, the polymer shell detaches from the nanoparticles, exposing a positively charged surface. This favors the internalization in human osteosarcoma cells, where the release of topotecan takes place, drastically enhancing the cytotoxic effect.

The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

PubMed

Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

2015-09-01

Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

Ultrasound-Guided Regional Anesthesia Simulation Training: A Systematic Review.

PubMed

Chen, Xiao Xu; Trivedi, Vatsal; AlSaflan, AbdulHadi A; Todd, Suzanne Clare; Tricco, Andrea C; McCartney, Colin J L; Boet, Sylvain

Ultrasound-guided regional anesthesia (UGRA) has become the criterion standard of regional anesthesia practice. Ultrasound-guided regional anesthesia teaching programs often use simulation, and guidelines have been published to help guide URGA education. This systematic review aimed to examine the effectiveness of simulation-based education for the acquisition and maintenance of competence in UGRA. Studies identified in MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC were included if they assessed simulation-based UGRA teaching with outcomes measured at Kirkpatrick level 2 (knowledge and skills), 3 (transfer of learning to the workplace), or 4 (patient outcomes). Two authors independently reviewed all identified references for eligibility, abstracted data, and appraised quality. After screening 176 citations and 45 full-text articles, 12 studies were included. Simulation-enhanced training improved knowledge acquisition (Kirkpatrick level 2) when compared with nonsimulation training. Seven studies measuring skill acquisition (Kirkpatrick level 2) found that simulation-enhanced UGRA training was significantly more effective than alternative teaching methods or no intervention. One study measuring transfer of learning into the clinical setting (Kirkpatrick level 3) found no difference between simulation-enhanced UGRA training and non-simulation-based training. However, this study was discontinued early because of technical challenges. Two studies examined patient outcomes (Kirkpatrick level 4), and one of these found that simulation-based UGRA training improved patient outcomes compared with didactic teaching. Ultrasound-guided regional anesthesia knowledge and skills significantly improved with simulation training. The acquired UGRA skills may be transferred to the clinical setting; however, further studies are required to confirm these changes translate to improved patient outcomes.

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

PubMed

Gvetadze, Shalva R; Xiong, Ping; Lv, Mingming; Li, Jun; Hu, Jingzhou; Ilkaev, Konstantin D; Yang, Xin; Sun, Jian

2017-03-01

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue ™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

PubMed

Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

2009-11-01

Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI.

PubMed

Song, I H; Althoff, C E; Hermann, K G; Scheel, A K; Knetsch, T; Burmester, G R; Backhaus, M

2009-01-01

To evaluate contrast-enhanced ultrasound (CE-US) as a monitoring tool to assess hypervascularisation of synovial processes in knee osteoarthritis (OA) treated with intra-articular injections of the bradykinin-receptor 2 antagonist icatibant compared to contrast-enhanced magnetic resonance imaging (CE-MRI). In a randomised, double-blind, placebo-controlled trial, 41 patients with painful knee OA underwent US (12.5 MHz for B-mode and 3-8 MHz for CE-US), and 36 of the patients underwent additional MRI (0.2T) at baseline and after 3 injections of the study drug (after a mean of 22.2 days). A total of 15 patients received placebo (group A), 12 patients 500 microg icatibant (group B) and 14 patients 2000 microg icatibant (group C). Pain and the synovial process (B-mode, power Doppler US (PD-US), CE-US, CE-MRI) were assessed at both time points. At baseline, the placebo group showed more activity in terms of effusion in the superior and lateral recess in ultrasound as well as in PD-US in the lateral recess. Pain improved significantly in all subgroups. Effect sizes were 0.43 (pain at rest) and 0.52 (pain during activity) in group B vs 0.48 and 1.11 in group C. There was no change of US and MRI parameters. We found moderate to good correlation (r) and kappa values (kappa) for effusion in the superior recess (r = 0.591, k = 0.453), effusion in the lateral recess (r = 0.304, k = 0.440) and contrast enhancement (r = 0.601, k = 0.242) between US and MRI. Our results show that CE-US and CE-MRI have good agreement in assessing inflammatory changes in knee OA. For the 41 patients with OA, an analgesic effect of icatibant could clearly be shown, especially for pain during activity in the high dose icatibant group. However, we could not find an anti-inflammatory effect of icatibant by CE-US compared to CE-MRI.

Combinational light emitting diode-high frequency focused ultrasound treatment for HeLa cell.

PubMed

Choe, Se-Woon; Park, Kitae; Park, Chulwoo; Ryu, Jaemyung; Choi, Hojong

2017-12-01

Light sources such as laser and light emitting diode or ultrasound devices have been widely used for cancer therapy and regenerative medicines, since they are more cost-effective and less harmful than radiation therapy, chemotherapy or magnetic treatment. Compared to laser and low intensity ultrasound techniques, light emitting diode and high frequency focused ultrasound shows enhanced therapeutic effects, especially for small tumors. We propose combinational light emitting diode-high frequency focused ultrasound treatment for human cervical cancer HeLa cells. Individual red, green, and blue light emitting diode light only, high frequency focused ultrasound only, or light emitting diode light combined with high frequency focused ultrasound treatments were applied in order to characterize the responses of HeLa cells. Cell density exposed by blue light emitting diode light combined with high frequency focused ultrasound (2.19 ± 0.58%) was much lower than that of cells exposed by red and green light emitting diode lights (81.71 ± 9.92% and 61.81 ± 4.09%), blue light emitting diode light (11.19 ± 2.51%) or high frequency focused ultrasound only (9.72 ± 1.04%). We believe that the proposed combinational blue light emitting diode-high frequency focused ultrasound treatment could have therapeutic benefits to alleviate cancer cell proliferation.

Ultrasound assisted process intensification of uricase and alkaline protease enzyme co-production in Bacillus licheniformis.