An Investigation of High Intensity Focused Ultrasound Thrombolysis

NASA Astrophysics Data System (ADS)

Wright, Cameron; Hynynen, Kullervo; Goertz, David

2011-09-01

Investigations into high intensity focused ultrasound (HIFU) thrombolysis in vitro and in vivo in a rabbit femoral artery thrombus model were performed. A 1.51 MHz focused transducer was used to treat clots with pulse lengths of 1-10 ms, acoustic powers of 1-300 W and exposure durations of 5-20 s. Our measurements indicate the creation of acoustic radiation force induced clot displacements are insufficient to mechanically fractionate clots, despite reaching displacements >100 μm. Only under the presence of inertial cavitation was HIFU able to disrupt clots. Cavitation thresholds of 160 W in vitro and 215 W in vivo were observed. In vitro, clots insonified at powers above the cavitation threshold eroded regions up to 2.5× the transducer beam width. Successful recanalization in vivo occurred in 5/20 cases for 1ms pulses at powers >215 W. 10 ms pulses created high incidences of symptomatic bleeding while 1 ms pulses did not. These results demonstrate treatment feasibility in vivo, although further work is required to understand the influence of different acoustic parameters on treatment outcome.

Effect of Low Frequency Ultrasound on Combined rt-PA and Eptifibatide Thrombolysis in Human Clots

PubMed Central

Meunier, Jason M.; Holland, Christy K.; Pancioli, Arthur M.; Lindsell, Christopher J.; Shaw, George J.

2009-01-01

Introduction Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Materials and Methods Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 μL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA+Epf), with or without ultrasound for 30 minutes at 37°C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. Results and Conclusions LR values for (−US) treated clots were 0.8±0.1(control), 1.8±0.3 (Epf), 1.5±0.2 (rt-PA), and 1.3±0.4 (rt-PA+Epf) (% clot width/minute) respectively. In comparison, the (+US) group exhibited LR values of 1.6±0.2 (control), 4.3±0.4 (Epf), 6.3±0.4 (rt-PA), and 4.6±0.6 (rt-PA+Epf). For (−US) treated clots, FCL was 6.0±0.8 (control), 9.2±2.5 (Epf), 15.6±1.7 (rt-PA), and 28.0±2.2% (rt-PA+Epf) respectively. FCL for (+US) clots was 13.5±2.4 (control), 20.7±6.4 (Epf), 44.4±3.6 (rt-PA) and 30.3±3.6% (rt-PA+Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of

Effects of varying duty cycle and pulse width on high-intensity focused ultrasound (HIFU)-induced transcranial thrombolysis.

PubMed

Hölscher, Thilo; Raman, Rema; Fisher, David J; Ahadi, Golnaz; Zadicario, Eyal; Voie, Arne

2013-01-01

The goal was to test the effects of various combinations of pulse widths (PW) and duty cycles (DC) on high-intensity focused ultrasound (HIFU)-induced sonothrombolysis efficacy using an in vitro flow model. An ExAblate™ 4000 HIFU headsystem (InSightec, Inc., Israel) was used. Artificial blood clots were placed into test tubes inside a human calvarium and exposed to pulsatile flow. Four different duty cycles were tested against four different pulse widths. For all study groups, an increase in thrombolysis efficacy could be seen in association with increasing DC and/or PW (p < 0.0001). Using transcranial HIFU, significant thrombolysis can be achieved within seconds and without the use of lytic drugs in vitro. Longer duty cycles in combination with longer pulse widths seem to have the highest potential to optimize clot lysis efficacy.

Effects of varying duty cycle and pulse width on high-intensity focused ultrasound (HIFU)-induced transcranial thrombolysis

PubMed Central

2013-01-01

The goal was to test the effects of various combinations of pulse widths (PW) and duty cycles (DC) on high-intensity focused ultrasound (HIFU)-induced sonothrombolysis efficacy using an in vitro flow model. An ExAblate™ 4000 HIFU headsystem (InSightec, Inc., Israel) was used. Artificial blood clots were placed into test tubes inside a human calvarium and exposed to pulsatile flow. Four different duty cycles were tested against four different pulse widths. For all study groups, an increase in thrombolysis efficacy could be seen in association with increasing DC and/or PW (p < 0.0001). Using transcranial HIFU, significant thrombolysis can be achieved within seconds and without the use of lytic drugs in vitro. Longer duty cycles in combination with longer pulse widths seem to have the highest potential to optimize clot lysis efficacy. PMID:25512862

Thrombolysis in Acute Ischaemic Stroke: An Update

PubMed Central

Robinson, Thompson; Zaheer, Zahid; Mistri, Amit K.

2011-01-01

Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke. While the licensed time window extends to 3h from symptom onset, recent data suggest that the trial window can be extended up to 4.5 h with overall benefit. Nonetheless, 'time is brain' and every effort must be made to reduce the time delay to thrombolysis. Intracranial haemorrhage is the major complication associated with thrombolysis, and key factors increasing risk of haemorrhage include increasing age, high blood pressure, diabetes and stroke severity. Currently, there is no direct evidence to support thrombolysis in patients >80 years of age, with a few case series indicating no overt harm. Identification of viable penumbra based on computed tomography/magnetic resonance imaging may allow future extension of the time window. Adjuvant transcranial Doppler ultrasound has the potential to improve reperfusion rates. While intra-arterial thrombolysis has been in vogue for a few decades, there is no clear advantage over intravenous thrombolysis. The evidence base for thrombolysis in specific situations (e.g. dissection, pregnancy) is inadequate, and individualized decisions are needed, with a clear indication to the patient/carer about the lack of direct evidence, and the risk-benefit balance. Patient-friendly information leaflets may facilitate the process of consent for thrombolysis. This article summarizes the recent advances in thrombolysis for acute ischaemic stroke. Key questions faced by clinicians during the decision-making process are answered based on the evidence available. PMID:23251746

Stable cavitation using acoustic phase-change dodecafluoropentane nanoparticles for coronary micro-circulation thrombolysis.

PubMed

Hu, Bo; Jiang, Nan; Zhou, Qing; Cao, Sheng; Gao, Shunji; Zhang, Binghong; Chen, Jinling; Guo, Ruiqiang

2018-06-11

The thrombolysis in micro-circulation after acute myocardial infarction has been an unsolved issue, as elimination effect of acute thrombolysis and primary intervention were unsatisfied. Stable cavitation using acoustic phase-change nanoparticles may have potential for thrombolysis. Therefore, we sought to investigate a novel treatment method with dodecafluoropentane (DDFP) nanoparticles for rapid and effective thrombolysis in an in-vitro artificial vascular system, as a mimicking preparation of coronary circulation. To simulate thrombus embolism in coronary circulation, an in-vitro artificial vascular system was established with cavitation effect using DDFP nanoparticles. For PBS blank control (group A), SonoVue microbubbles (group B) and DDFP nanoparticles (group C), the durations for cavitation effect were recorded and the thrombolysis efficiency with low intensity focused ultrasound irradiation in the in-vitro vascular system were analyzed with weight loss and pathological changes of thrombus before and after thrombolysis. The optimal conditions for acoustic cavitation effect were power of 6 W for 20 min by ultrasound irradiation at 37 °C. The weight loss and weight loss rates of thrombus in group C (189.4 ± 30.2 mg and 34.2 ± 5.7%) were higher than those in group A (30.2 ± 16.0 mg and 5.2 ± 2.1%) and group B (84.0 ± 20.4 mg and 14.6 ± 1.5%) (P < 0.01, all). The duration for cavitation effect in group C (32.8 ± 3.9 min) was also longer than those in group A (0.0 ± 0.0 min) and group B (5.3 ± 0.3 min) (P < 0.01, all). By stable and sustaining cavitation in targeted area, DDFP nanoparticles with ultrasound irradiation have significantly increased the thrombolysis efficiency, which has provided a powerful experimental foundation for potential coronary thrombolysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of Transcranial Doppler Ultrasound on Logistics and Outcomes in Stroke Thrombolysis: Results From the SITS-ISTR.

PubMed

Mazya, Michael V; Ahmed, Niaz; Azevedo, Elsa; Davalos, Antoni; Dorado, Laura; Karlinski, Michal; Lorenzano, Svetlana; Neumann, Jiří; Toni, Danilo; Moreira, Tiago P

2018-07-01

Diagnostic transcranial Doppler ultrasound (TCD) is commonly used in patients with acute stroke before or during treatment with intravenous thrombolysis (IVT). We aimed to assess how much TCD delays IVT initiation and whether TCD influences outcomes. We analyzed data from the SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) collected from December 2002 to December 2011. Outcomes were door-to-needle time, symptomatic intracerebral hemorrhage, functional outcome per the modified Rankin Scale, and mortality at 3 months. In hospitals performing any TCD pre-IVT, 1701 of 11 265 patients (15%) had TCD before IVT initiation. Door-to-needle time was higher in patients with pre-IVT TCD (74 versus 60 minutes; P <0.001). At hospitals performing any TCD during IVT infusion, of 9044 patients with IVT, 747 were examined with TCD during IVT. No treatment delay was seen with TCD during IVT. After multivariate adjustment, TCD during IVT was independently associated with modestly increased excellent functional outcome (modified Rankin Scale, 0-1; adjusted odds ratio, 1.28; 95% confidence interval, 1.06-1.55; P =0.012) and lower mortality (adjusted odds ratio, 0.73; 95% confidence interval, 0.55-0.95; P =0.022). We recommend that TCD, if performed, should be done during IVT infusion, to avoid treatment delay. The association of hyperacute TCD with beneficial outcomes suggests potential impact on patient management, which warrants further study. © 2018 American Heart Association, Inc.

Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Inferior Vena Cava Thrombosis After an Orthotopic Liver Transplant

PubMed Central

Latchana, Nicholas; Dowell, Joshua D.; Taani, Jamal Al; Michaels, Anthony; Elkhammas, Elmadhi; Black, Sylvester M.

2015-01-01

Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver transplant that is associated with a high rate of retransplant and mortality. There is no consensus regarding the optimal therapeutic strategy. Surgical management, including thrombectomy with revision of the cavocaval anastomosis, has been described. With the use of endovascular therapies, several minimally invasive approaches are available that are effective and avoid the high morbidity associated with reoperative surgery. We describe our successful experience using an approach after a liver transplant in which the inferior vena cava thrombosis in a patient presenting with acute renal failure, anorexia, weight loss, and fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform in conjunction with systemic anticoagulation. PMID:24918871

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound.

PubMed

Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K

2014-02-01

Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

Catheter-directed, ultrasound-assisted thrombolysis is a safe and effective treatment for pulmonary embolism, even in high-risk patients.

PubMed

Lee, Kristen A; Cha, Andrew; Kumar, Mark H; Rezayat, Combiz; Sales, Clifford M

2017-03-01

We sought to assess the early success and safety of catheter-directed, ultrasound-assisted (CDUA) thrombolysis for acute pulmonary embolism (PE) in patients deemed to be "high risk" for thrombolytic therapy. A retrospective evaluation of patients who underwent CDUA pulmonary thrombolysis in our practice during 39 months is reported. There were 91 patients considered, all of whom presented with acute PE as diagnosed by computed tomography angiography. The ratio of the right ventricle to left ventricle diameter (RV axial :LV axial ) was noted, as were preprocedure pulmonary artery pressures (PAPs). Demographic data, significant medical history, and procedure details were recorded. Standard thrombolysis protocol was followed (1 mg of tissue plasminogen activator per hour per catheter after an initial 2-mg bolus per catheter). Minitab 17 (Minitab Inc, State College, PA) was used for data analysis. There were 91 patients who had a computed tomography diagnosis of acute PE and pulmonary hypertension (PAP >25 mm Hg). Seventeen patients (19%) were deemed to be at high risk for bleeding, predicted by recent hemorrhage, major surgery within 3 weeks, acute myocardial infarction, and cardiac arrest with cardiopulmonary resuscitation within 1 week. The high-risk patients in our study were noted to have higher RV:LV ratios and lower oxygen saturations on admission (P < .05). On computed tomography angiography, the mean pretherapy RV axial :LV axial ratio was 1.5 ± 0.4. The mean pretherapy PAP was 56.2 ± 15.2 mm Hg. After 18.5 ± 3.5 hours of thrombolysis, the mean post-therapy PAP was 34.3 ± 10.4 mm Hg, with a pressure drop of 21.9 ± 4.8 mm Hg (39% decrease; P < .001). In total, seven patients (8%) suffered bleeding complications that required intervention-four gastrointestinal bleeds, a rectus sheath hematoma, and one gross hematuria. Three of the seven complications occurred in the high-risk group (3/17) and the other four in the general population of patients (4

76 FR 31616 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DD. Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes... al. Pulsed-high intensity focused ultrasound enhances thrombolysis in an in vitro model. Radiology...

Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis.

PubMed

Kim, Jinwook; Lindsey, Brooks D; Chang, Wei-Yi; Dai, Xuming; Stavas, Joseph M; Dayton, Paul A; Jiang, Xiaoning

2017-06-14

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

Investigations on the destruction of ultrasound contrast agents: Fragmentation thresholds, inertial cavitation, and bioeffects

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang

Ultrasound contrast agents (UCA) have shown great potential in both diagnostic and therapeutic applications recently. To fully explore the possible applications and the safety concerns of using UCA, a complete understanding of the UCA responses to various acoustic fields is necessary. Therefore, we performed a series of experiments and simulations to investigate the various acoustic properties of UCA with different gases and shells. We also investigated the mechanisms of some UCA-enhanced bioeffects including thrombolysis, hemolysis and high-intensity focused ultrasound (HIFU) tumor ablation. Two pressure thresholds were found: the fragmentation threshold and continuous inertial cavitation (IC) threshold. At the fragmentation threshold, bubbles were destroyed and the released gas dissolved in the surrounding solution at a rate which depended on the bubble's initial size and type of gas. The continuous IC threshold occurred at a higher pressure, where fragments of destroyed UCA (derivative bubbles) underwent violent inertial collapse; the period of activity depending on acoustic parameters such as frequency, pressure, pulse length, and pulse repetition frequency (PRF). Different UCA had different threshold pressures and demonstrated different magnitudes of IC activity after destruction. The amount of derivative bubbles generated by IC was determined by several acoustic parameters including pressure, pulse length and PRE For the same acoustic energy delivered, longer pulses generated more bubbles. More IC could be induced if the derivative bubbles could survive through the 'off' period of the pulsed ultrasound waves, and served as nuclei for the subsequent IC. In therapeutic applications, evidences of IC activity were recorded during the hemolysis, thrombolysis, and the lesion-formation processes with UCA. Hemolysis and thrombolysis were highly correlated to the presence of ultrasound and UCA, and correlated well with the amount of the IC activity. Finally, the

Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis.

PubMed

Carr, Susan J; Wang, Xia; Olavarria, Veronica V; Lavados, Pablo M; Rodriguez, Jorge A; Kim, Jong S; Lee, Tsong-Hai; Lindley, Richard I; Pontes-Neto, Octavio M; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K; Woodward, Mark; Chalmers, John; Anderson, Craig S; Robinson, Thompson G

2017-09-01

Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m 2 ) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2-6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models. Compared with patients with normal renal function (>90 mL/min per 1.73 m 2 ), those with severe RD (<30 mL/min per 1.73 m 2 ) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89-4.82; P =0.04 for trend); every 10 mL/min per 1.73 m 2 lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.70; P =0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P =0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review.

PubMed

Elbasty, Ahmed; Metcalf, James

2017-12-01

Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review

PubMed Central

Elbasty, Ahmed; Metcalf, James

2017-01-01

Purpose Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. Materials and Methods MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration’s tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Results Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. Conclusion CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured. PMID:29354622

Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer.

PubMed

Morelli, Girolamo; Pagni, Riccardo; Mariani, Chiara; Minervini, Riccardo; Morelli, Andrea; Gori, Francesco; Ferdeghini, Ezio Maria; Paterni, Marco; Mauro, Eva; Guidi, Elisa; Armillotta, Nicola; Canale, Domenico; Vitti, Paolo; Caramella, Davide; Minervini, Andrea

2011-06-01

We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p <0.005 and <0.001, respectively). The detection rate of standard plus contrast or vardenafil enhanced power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological

Ultrasound-enhanced drug delivery for cancer.

PubMed

Mo, Steven; Coussios, Constantin-C; Seymour, Len; Carlisle, Robert

2012-12-01

Ultrasound, which has traditionally been used as a diagnostic tool, is increasingly being used in non-invasive therapy and drug delivery. Of particular interest to this review is the rapidly accumulating evidence that ultrasound may have a key role to play both in improving the targeting and the efficacy of drug delivery for cancer. Currently available ultrasound-triggerable vehicles are first described, with particular reference to the ultrasonic mechanism that can activate release and the suitability of the size range of the vehicle used for drug delivery. Further mechanical and thermal effects of ultrasound that can enhance extravasation and drug distribution following release are then critically reviewed. Acoustic cavitation is found to play a potentially key role both in achieving targeted drug release and enhanced extravasation at modest pressure amplitudes and acoustic energies, whilst simultaneously enabling real-time monitoring of the drug delivery process. The next challenge in ultrasound-enhanced drug delivery will thus be to develop a new generation of drug-carrying nanoparticles which are of the right size range for delivery to tumours, yet still capable of achieving initiation of cavitation activity and drug release at modest acoustic pressures and energies that have no safety implications for the patient.

Targeted thrombolysis by using of magnetic mesoporous silica nanoparticles.

PubMed

Wang, Mingqi; Zhang, Jixi; Yuan, Ziming; Yang, Wenzhi; Wu, Qiang; Gu, Hongchen

2012-08-01

Thrombolytics inevitably led to the risk of hemorrhagic complications due to their non-specific plasminogen activation in treatment of thrombosis. The aim of this study was to determine whether a kind of superparamagnetic mesoporous silica nanoparticle with expanded pore size could achieve effectively targeted thrombolysis. The magnetic mesoporous silica nanoparticles (M-MSNs) with the pore size of 6 nm were prepared by method of the surfactant templating on nano magnetic particles. We investigated the feasibility and efficacy of target thrombolysis with the resultant spheres through fibrin agarose plate assay (FAPA) and a dynamic flow system in vitro. It displayed a 30-fold enhancement of urokinase (UK) loading capacity over the particles without mesoporous layer or the magnetic spheres with mesopores of 3.7 nm. A sustained release behavior was observed due to its larger pore size, higher surface area and narrow mesopore channals contrast to non-mesoporous and small mesopore of 3.7 nm controls. Meanwhile, fibrin agarose plate assay revealed that UK/M-MSNs exhibited a more rapid growth rate of thrombolysis even lasting for 3 days. Additionally, flow model test in vitro suggested this kind of nanoparticle complex enhanced the thrombolysis efficacy by 3.5 fold over the same amount of native UK in 30 min. When compared to non-mesoporous and small mesopore controls, it also represented an extremely higher lysis efficiency (ANOVA, P < 0.01) and a shorter reperfusion time (ANOVA, P < 0.001). Such a magnetic mesoporous silica nanoparticle carrier was expected to be further studied for targeted thrombolytic therapy.

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.

[Prehospital thrombolysis during cardiopulmonary resuscitation].

PubMed

Spöhr, F; Böttiger, B W

2005-02-01

Although prehospital cardiac arrest has an incidence of 40-90/100,000 inhabitants per year, there has been a lack of therapeutic options to improve the outcome of these patients. Of all cardiac arrests, 50-70% are caused by acute myocardial infarction (AMI) or massive pulmonary embolism (PE). Thrombolysis has been shown to be a causal and effective therapy in patients with AMI or PE who do not suffer cardiac arrest. In contrast, experience with the use of thrombolysis during cardiac arrest has been limited. Thrombolysis during cardiopulmonary resuscitation (CPR) acts directly on thrombi or emboli causing AMI or PE. In addition, experimental studies suggest that thrombolysis causes an improvement in microcirculatory reperfusion after cardiac arrest. In-hospital and prehospital case series and clinical studies suggest that thrombolysis during CPR may cause a restoration of spontaneous circulation and survival even in patients that have been resuscitated conventionally without success. In addition, there is evidence for an improved neurological outcome in patients receiving a thrombolytic therapy during during CPR. A large randomized, double-blind multicenter trial that has started recently is expected to show if this new therapeutic option can generally improve the prognosis of patients with cardiac arrest.

Development of endovascular vibrating polymer actuator probe for mechanical thrombolysis: a phantom study.

PubMed

Choi, Seung Hong; Yoon, Bye-Ri; Oh, Jin Sun; Han, Moon Hee; Lee, Jang Yeol; Cho, Hye Rim; Kim, Moon June; Rhee, Kyehan; Jho, Jae Young

2011-01-01

In this study, we propose a new method for enhancement of intraarterial thrombolysis using an ionic polymer-metal composite (IPMC) actuator. The purpose of this study was to test the mechanical thrombolysis efficiency of IPMC actuators and evaluate the endovascular vibrating polymer actuator probe for mechanical thrombolysis in a phantom model; 2 × 1 × 15 mm (2 mm in width, 1 mm in thickness, and 15 mm in length) and 0.8 × 0.8 × 10 mm (0.8 mm in width, 0.8 mm in thickness, and 10 mm in length) IPMC actuators were fabricated by stacking five and four Nafion-117 films, respectively. We manufactured the endovascular vibrating polymer actuator probe, for which thrombolysis efficiency was tested in a vascular phantom. The phantom study using 2 × 1 × 15 mm IPMC actuators showed that 5 Hz actuation is the optimal frequency for thrombolysis under both 2 and 3 V, when blood clot was not treated with rtPA, and when exposed to rtPA, IPMC actuators under the optimized condition (3 V, 5 Hz, and 5 min) significantly increased the thrombolysis degree compared with control and other experimental groups (p < 0.05). In addition, 0.8 × 0.8 × 10 mm IPMC actuators also revealed a significantly higher thrombolysis degree under the optimized condition than the control and rtPA only groups (p < 0.05). Finally, the fabricated probe using 0.8 × 0.8 × 10 mm IPMC actuators also incurred higher thrombolysis degree under the optimized condition than the control and rtPA only groups (p < 0.05). A vibrating polymer actuator probe is a feasible device for intravascular thrombolysis, and further study in an animal model is warranted.

Ultrasound enhances retrovirus-mediated gene transfer.

PubMed

Naka, Toshio; Sakoda, Tsuyoshi; Doi, Takashi; Tsujino, Takeshi; Masuyama, Tohru; Kawashima, Seinosuke; Iwasaki, Tadaaki; Ohyanagi, Mitsumasa

2007-01-01

Viral vector systems are efficient for transfection of foreign genes into many tissues. Especially, retrovirus based vectors integrate the transgene into the genome of the target cells, which can sustain long term expression. However, it has been demonstrated that the transduction efficiency using retrovirus is relatively lower than those of other viruses. Ultrasound was recently reported to increase gene expression using plasmid DNA, with or without, a delivery vehicle. However, there are no reports, which show an ultrasound effect to retrovirus-mediated gene transfer efficiency. Retrovirus-mediated gene transfer systems were used for transfection of 293T cells, bovine aortic endothelial cells (BAECs), rat aortic smooth muscle cells (RASMCs), and rat skeletal muscle myoblasts (L6 cells) with beta-galactosidase (beta-Gal) genes. Transduction efficiency and cell viability assay were performed on 293T cells that were exposed to varying durations (5 to 30 seconds) and power levels (1.0 watts/cm(2) to 4.0 watts/cm(2)) of ultrasound after being transduced by a retrovirus. Effects of ultrasound to the retrovirus itself was evaluated by transduction efficiency of 293T cells. After exposure to varying power levels of ultrasound to a retrovirus for 5 seconds, 293T cells were transduced by a retrovirus, and transduction efficiency was evaluated. Below 1.0 watts/cm(2) and 5 seconds exposure, ultrasound showed increased transduction efficiency and no cytotoxicity to 293T cells transduced by a retrovirus. Also, ultrasound showed no toxicity to the virus itself at the same condition. Exposure of 5 seconds at the power of 1.0 watts/cm(2) of an ultrasound resulted in significant increases in retrovirus-mediated gene expression in all four cell types tested in this experiment. Transduction efficiencies by ultrasound were enhanced 6.6-fold, 4.8-fold, 2.3-fold, and 3.2-fold in 293T cells, BAECs, RASMCs, and L6 cells, respectively. Furthermore, beta-Gal activities were also increased

Contrast-enhanced and targeted ultrasound.

PubMed

Postema, Michiel; Gilja, Odd Helge

2011-01-07

Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.

Contrast-enhanced and targeted ultrasound

PubMed Central

Postema, Michiel; Gilja, Odd Helge

2011-01-01

Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested. PMID:21218081

Thrombus resolution and right ventricular functional recovery using ultrasound-accelerated thrombolysis in acute massive and submassive pulmonary embolism.

PubMed

Ozcinar, Evren; Cakici, Mehmet; Dikmen Yaman, Nur; Baran, Cagdas; Aliyev, Anar; Inan, Bahadir; Durdu, Serkan; Akar, Ahmet R; Sirlak, Mustafa

2017-10-01

This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured. The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding. This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.

Ultrasound-enhanced localized chemotherapy of drug-sensitive and multidrug resistant tumors

NASA Astrophysics Data System (ADS)

Rapoport, Natalya Y.; Gao, Zhonggao; Kamaev, Pavel; Christensen, Douglas A.

2006-05-01

A new modality of targeted tumor chemotherapy is based on the drug encapsulation in polymeric nanoparticles followed by a localized release at the tumor site triggered by focused ultrasound. Effect of 1 MHz and 3 MHz unfocused ultrasound applied locally to the tumor on the Doxorubicin (DOX) biodistribution and tumor growth rates was measured for ovarian carcinoma tumors in nu/nu mice. The bioeffects of ultrasound were investigated on the systemic and cellular levels. Growth rates of A2780 ovarian carcinoma tumors were substantially reduced by combining micellar drug delivery with tumor irradiation. Ultrasound effect was not thermal as manifested by intratumoral temperature measurements during sonication. Biodistribution studies showed that ultrasound did not enhance micelle extravasation. Main mechanisms of the ultrasound-enhanced chemotherapy included (i) passive targeting of drug-loaded micelles to the tumor interstitium; (ii) ultrasound-triggered localized drug release from micelles in the tumor volume; (iii) enhanced micelle and drug diffusion through the tumor interstitium; and (iv) ultrasound-triggered cell membrane damage resulting in the enhanced micelle and drug uptake by tumor cells.

Outcomes and predictors of failure of thrombolysis for iliofemoral deep venous thrombosis.

PubMed

Avgerinos, Efthymios D; Hager, Eric S; Naddaf, Abdallah; Dillavou, Ellen; Singh, Michael; Chaer, Rabih A

2015-01-01

Catheter-directed thrombolysis (CDT) with adjunctive mechanical techniques, when successful, is reported to alleviate symptoms of acute iliofemoral deep venous thrombosis (IFDVT) and to lower the occurrence of the post-thrombotic syndrome (PTS). This study aimed to determine longer term outcomes of catheter-based interventions for IFDVT and to identify predictors of immediate and mid-long-term failures that would guide optimal patient selection. Consecutive patients who underwent CDT or pharmacomechanical thrombolysis for IFDVT between May 2007 and March 2013 were identified from a prospectively maintained database. Assessment of predictors of immediate periprocedural failure was based on the degree of clot lysis (≤ 50% vs >50%) and 30-day recurrence of DVT. Long-term anatomic and clinical failures and outcomes were assessed by ultrasound imaging of the lysed segments and Villalta score (≥ 5 vs <5). Survival analysis was used to assess primary patency and PTS morbidity. Multivariate binary logistic and Cox regression models were used to determine predictors of anatomic and clinical failures. During the study period, 93 patients (118 limbs; mean age, 49.4 ± 16.2 years; 47 women) with symptoms averaging 11.1 ± 9.6 days in duration were treated with various combinations of CDT or pharmacomechanical thrombolysis; in 52 (56%), at least one iliocaval stent was deployed. Immediate treatment failure was seen in 11 patients (12%) predicted by the preoperative indication "phlegmasia" (odds ratio, 3.12; P = .042) and recent surgery (odds ratio, 19.6; P = .018). At a mean ultrasonographic follow-up of 16 ± 14 months (range, 1-65 months), six more patients sustained a rethrombosis, accounting for an overall 3-year primary patency of 72.1%. In the long-term model, loss of primary patency was associated with recent surgery (hazard ratio [HR], 4.04; P = .023), malignant disease (HR, 6.75; P = .016), and incomplete thrombolysis (≤ 50%) (HR, 5.83; P < .001). By

Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

NASA Astrophysics Data System (ADS)

Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

2009-04-01

Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

Pharmacomechanical thrombolysis with a rotator thrombolysis device in iliofemoral deep venous thrombosis.

PubMed

Karahan, Oguz; Kutas, H Barıs; Gurbuz, Orcun; Tezcan, Orhan; Caliskan, Ahmet; Yavuz, Celal; Demirtas, Sinan; Mavitas, Binali

2016-10-01

Deep venous thrombosis (DVT) is a life-threatening and morbid pathology. This study aimed to investigate the efficacy of an early thrombolysis procedure using a rotator thrombolysis device. Sixty-seven patients with acute proximal DVT were enrolled in the study. Patients' data were recorded retrospectively. Initially, an infrarenal retrievable vena cava filter was placed through the femoral vein. Then, a rotator thrombolysis device and a thrombolytic agent injection were applied to the occluded segments of the deep veins by puncturing the popliteal vein. The identified reasons were trauma (43.3%), pregnancy (20.9%), undiagnosed (11.9%), major surgical operation (10.5%), immobilization (7.5%), and malignancy (5.9%). Immediate total recanalization was conducted in all patients, and the leg diameters returned to normal ranges in the early postoperative period. Hospital mortality or severe complications were not detected. New thrombolytic devices seem to reduce in-hospital mortality risks and may potentially decrease post-thrombotic morbidity. © The Author(s) 2015.

Vascular applications of contrast-enhanced ultrasound imaging.

PubMed

Mehta, Kunal S; Lee, Jake J; Taha, Ashraf G; Avgerinos, Efthymios; Chaer, Rabih A

2017-07-01

Contrast-enhanced ultrasound (CEUS) imaging is a powerful noninvasive modality offering numerous potential diagnostic and therapeutic applications in vascular medicine. CEUS imaging uses microbubble contrast agents composed of an encapsulating shell surrounding a gaseous core. These microbubbles act as nearly perfect intravascular reflectors of ultrasound energy and may be used to enhance the overall contrast and quality of ultrasound images. The purpose of this narrative review is to survey the current literature regarding CEUS imaging and discuss its diagnostic and therapeutic roles in current vascular and selected nonvascular applications. The PubMed, MEDLINE, and Embase databases were searched until July 2016 using the PubMed and Ovid Web-based search engines. The search terms used included contrast-enhanced, microbubble, ultrasound, carotid, aneurysm, and arterial. The diagnostic and therapeutic utility of CEUS imaging has grown exponentially, particularly in the realms of extracranial carotid arterial disease, aortic disease, and peripheral arterial disease. Studies have demonstrated that CEUS imaging is diagnostically superior to conventional ultrasound imaging in identifying vessel irregularities and measuring neovascularization to assess plaque vulnerability and end-muscle perfusion. Groups have begun to use microbubbles as agents in therapeutic applications for targeted drug and gene therapy delivery as well as for the enhancement of sonothrombolysis. The emerging technology of microbubbles and CEUS imaging holds considerable promise for cardiovascular medicine and cancer therapy given its diagnostic and therapeutic utility. Overall, with proper training and credentialing of technicians, the clinical implications are innumerable as microbubble technology is rapidly bursting onto the scene of cardiovascular medicine. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days

Model for Porosity Changes Occurring during Ultrasound-Enhanced Transcorneal Drug Delivery.

PubMed

Hariharan, Prasanna; Nabili, Marjan; Guan, Allan; Zderic, Vesna; Myers, Matthew

2017-06-01

Ultrasound-enhanced drug delivery through the cornea has considerable therapeutic potential. However, our understanding of how ultrasound enhances drug transport is poor, as is our ability to predict the increased level of transport for given ultrasound parameters. Described here is a computational model for quantifying changes in corneal porosity during ultrasound exposure. The model is calibrated through experiments involving sodium fluorescein transport through rabbit cornea. Validation was performed using nylon filters, for which the properties are known. It was found that exposure to 800-kHz ultrasound at an intensity 2 W/cm 2 for 5 min increased the porosity of the epithelium by a factor of 5. The model can be useful for determining the extent to which ultrasound enhances the amount of drug transported through biological barriers, and the time at which a therapeutic dose is achieved at a given location, for different drugs and exposure strategies. Published by Elsevier Inc.

How best to obtain consent to thrombolysis: Individualized decision-making.

PubMed

Gong, Jingjing; Zhang, Yan; Feng, Jun; Zhang, Weiwei; Yin, Weimin; Wu, Xinhuai; Hou, Yanhong; Huang, Yonghua; Liu, Hongyun; Miao, Danmin

2016-03-15

To investigate the factors that influence the preferences of patients and their proxies concerning thrombolytic therapy and to determine how best to convey information. A total of 613 participants were randomly assigned to a positively or negatively framed group. Each participant completed a series of surveys. We applied latent class analysis (LCA) to explore participants' patterns of choices of thrombolysis and to classify the participants into different subgroups. Then we performed regression analyses to investigate predictors of classification of the participants into each subgroup and to establish a thrombolytic decision-making model. LCA indicated an optimal 3-subgroup model comprising intermediate, favorable to thrombolysis, and aversion to thrombolysis subgroups. Multiple regression analysis revealed that 10 factors predicted assignment to the intermediate subgroup and 4 factors predicted assignment to the aversion to thrombolysis subgroup compared with the favorable to thrombolysis subgroup. The χ(2) tests indicated that the information presentation format and the context of thrombolysis influenced participants' choices of thrombolysis and revealed a framing effect in different subgroups. The preference for thrombolysis was influenced by the positive vs negative framing scenarios, the format of item presentation, the context of thrombolysis, and individual characteristics. Inconsistent results may be due to participant heterogeneity and the evaluation of limited factors in previous studies. Based on a decision model of thrombolysis, physicians should consider the effects of positive vs negative framing and should seek a neutral tone when presenting the facts, providing an important reference point for health persuasion in other clinical domains. © 2016 American Academy of Neurology.

Reducing call-to-needle times: the critical role of pre-hospital thrombolysis.

PubMed

Smith, J A L; Jennings, K P; Anderson, E A; Green, P; Hillis, G S

2004-10-01

Current guidelines recommend that patients with acute myocardial infarction should receive thrombolysis within 60 min of seeking professional help. To compare current rates of pre-hospital thrombolysis in Grampian with historical data, and assess the effect of pre-hospital thrombolysis on the proportion of patients achieving 'call-to-needle' times within national guidelines. Prospective audit. Data were collected on all patients (n=535) admitted to the coronary care unit and thrombolysed, either in hospital or in the community from July 2000 to June 2002, using standardized forms. One hundred and thirty-three patients (25%) received pre-hospital thrombolysis and 402 (75%) received in-hospital thrombolysis. This compares with a 19% (195/1046) pre-hospital thrombolysis rate in the mid-1990s (p=0.005). Median 'call-to-needle' times were 45 min for pre-hospital thrombolysis and 105 min for patients who received in-hospital thrombolysis (p < 0.001). Only 24% (96/396) of patients receiving in-hospital thrombolysis were treated within the recommended guideline, vs. 79% (88/111) of pre-hospital thrombolysis patients (p <0.001). Pre-hospital thrombolysis rates in Grampian are increasing. Administration of thrombolysis in the community greatly increases the proportion of patients achieving a 'call-to-needle' time of 60 min, with a median time saving of approximately 1 h.

A preliminary evaluation of self-made nanobubble in contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

Li, Chunfang; Wu, Kaizhi; Li, Jing; Liu, Haijuan; Zhou, Qibing; Ding, Mingyue

2014-03-01

Nanoscale bubbles (nanobubbles) have been reported to improve contrast in tumor-targeted ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, a self-made nanobubble ultrasound contrast agent was preliminarily characterized and evaluated in-vitro and in-vivo. Fundamental properties such as morphology appearance, size distribution, zeta potential, bubble concentration (bubble numbers per milliliter contrast agent suspension) and the stability of nanobubbles were assessed by light microscope and particle sizing analysis. Then the concentration intensity curve and time intensity curves (TICs) were acquired by ultrasound imaging experiment in-vitro. Finally, the contrast-enhanced ultrasonography was performed on rat to investigate the procedure of liver perfusion. The results showed that the nanobubbles had good shape and uniform distribution with the average diameter of 507.9 nm, polydispersity index (PDI) of 0.527, and zeta potential of -19.17 mV. Significant contrast enhancement was observed in in-vitro ultrasound imaging, demonstrating that the self-made nanobubbles can enhance the contrast effect of ultrasound imaging efficiently in-vitro. Slightly contrast enhancement was observed in in-vivo ultrasound imaging, indicating that the nanobubbles are not stable enough in-vivo. Future work will be focused on improving the ultrasonic imaging performance, stability, and antibody binding of the nanoscale ultrasound contrast agent.

Ultrasound image-guided therapy enhances antitumor effect of cisplatin.

PubMed

Sasaki, Noboru; Kudo, Nobuki; Nakamura, Kensuke; Lim, Sue Yee; Murakami, Masahiro; Kumara, W R Bandula; Tamura, Yu; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2014-01-01

The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.

Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis.

PubMed

Shaw, George J; Dhamija, Ashima; Bavani, Nazli; Wagner, Kenneth R; Holland, Christy K

2007-06-07

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Deltam(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E(eff) of 42.0 +/- 0.9 kJ mole(-1). E(eff) approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole(-1). A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.

Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis

NASA Astrophysics Data System (ADS)

Shaw, George J.; Dhamija, Ashima; Bavani, Nazli; Wagner, Kenneth R.; Holland, Christy K.

2007-06-01

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T <= 35 °C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Δm(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy Eeff of 42.0 ± 0.9 kJ mole-1. Eeff approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole-1. A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.

Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects

PubMed Central

Chama, Abdoulkadri; Subramanian, Anuradha; Viljoen, Hendrik J.

2017-01-01

This study presents two novel theoretical models to elucidate frequency sensitive nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast to the typical 1.5 MHz pulsed ultrasound regime, our group previously experimentally confirmed that ultrasound stimulation of anchored chondrocytes at resonant frequency maximized gene expression of load inducible genes which are regulatory markers for cellular response to external stimuli. However, ERK phosphorylation displayed no frequency dependency, suggesting that the biochemical mechanisms involved in enhanced gene expression is downstream of ERK phosphorylation. To elucidate such underlying mechanisms, this study presents a theoretical model of an anchored cell, representing an in vitro chondrocyte, in an ultrasound field. The model results showed that the mechanical energy storage is maximized at the chondrocyte’s resonant frequency and the energy density in the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical model was developed to link the mechanical stimulation of ultrasound and the increased mechanical energy density in the nucleus to the downstream targets of the ERK pathway. This study showed for the first time that ultrasound stimulation induces frequency dependent gene expression as a result of altered rates of transcription factors binding to chromatin. PMID:28763448

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

PubMed

Vedantham, Suresh; Goldhaber, Samuel Z; Julian, Jim A; Kahn, Susan R; Jaff, Michael R; Cohen, David J; Magnuson, Elizabeth; Razavi, Mahmood K; Comerota, Anthony J; Gornik, Heather L; Murphy, Timothy P; Lewis, Lawrence; Duncan, James R; Nieters, Patricia; Derfler, Mary C; Filion, Marc; Gu, Chu-Shu; Kee, Stephen; Schneider, Joseph; Saad, Nael; Blinder, Morey; Moll, Stephan; Sacks, David; Lin, Judith; Rundback, John; Garcia, Mark; Razdan, Rahul; VanderWoude, Eric; Marques, Vasco; Kearon, Clive

2017-12-07

The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. Among patients

Reasons and evolution of non-thrombolysis in acute ischaemic stroke

PubMed Central

Reiff, T; Michel, P

2017-01-01

Introduction Despite increasing evidence of its efficacy in advanced age or in mild or severe strokes, intravenous thrombolysis remains underused for acute ischaemic stroke (AIS). Our aim was to obtain an updated view of reasons for non-thrombolysis and to identify its changing patterns over time. Methods This is a retrospective study of prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) from the years 2003–2011. Patients admitted with acute stroke in the past 24 hours who had not had thrombolysis were identified; reasons for non-thrombolysis documented in the prospectively entered data were tabulated and analysed for the group as a whole. Data were analysed for the years 2003–2006 and 2007 forward because of changes in contraindications. A subgroup of patients who arrived within the treatment window ≤180 min was separately analysed for reasons for non-thrombolysis. Predictors of non-thrombolysis were investigated via multivariate regression analyses. Results In the 2019 non-thrombolysed patients the most frequent reasons for non-thrombolysis were admission delays (66.3%), stroke severity (mostly mild) (47.9%) and advanced age (14.1%); 55.9% had more than one exclusion criterion. Among patients arriving ≤180 min after onset, the main reasons were stroke severity and advanced age. After 2006, significantly fewer patients were excluded because of age (OR 2.65, p<0.001) or (mostly mild) stroke severity (OR 10.56, p=0.029). Retrospectively, 18.7% of all non-thrombolysed patients could have been treated because they only had relative contraindications. Conclusion Onset-to-admission delays remain the main exclusion criterion for thrombolysis. Among early arrivals, relative contraindications such as minor stroke severity and advanced age were frequent. Thrombolysis rate increased with the reduction of thrombolysis restrictions (eg, age and stroke severity). PMID:27797870

Endovascular Thrombolysis Using Monteplase for Non-chronic Deep Venous Thrombosis

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

Yamagami, Takuji, E-mail: yamagami@koto.kpu-m.ac.jp; Yoshimatsu, Rika, E-mail: rika442@koto.kpu-m.ac.jp; Tanaka, Osamu, E-mail: otanaka@koto.kpu-m.ac.jp

This study was designed to evaluate the usefulness of endovascular thrombolysis using monteplase for deep venous thrombosis (DVT). Between December 2005 and October 2009, at our institution nine endovascular thrombolysis treatments with monteplase were performed for symptomatic DVT in eight patients (6 women, 2 men; mean age, 56 (range, 15-80) years). In all, systemic anticoagulation administered by the peripheral intravenous route with heparin and/or thrombolysis with urokinase followed by anticoagulation with orally administered warfarin had been performed, and subsequently six endovascular treatments without monteplase were administered. However, DVT persisted, and endovascular treatments with monteplase were tried. In six (67%) ofmore » the nine procedures, DVT completely or almost completely disappeared after endovascular thrombolysis with monteplase. Mean dose of monteplase used was 2,170,000 IU. There was only one procedure-related complication. In one patient, just after thrombolysis with monteplase, bleeding at the puncture site and gingival bleeding occurred. Bleeding was stopped by manual astriction only. Endovascular thrombolysis with monteplase may be an effective treatment for DVT, even in cases resistant to traditional systemic anticoagulation and thrombolysis and endovascular procedures without monteplase.« less

Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED).

PubMed

Anderson, Craig S; Woodward, Mark; Arima, Hisatomi; Chen, Xiaoying; Lindley, Richard I; Wang, Xia; Chalmers, John

2015-12-01

The ENhanced Control of Hypertension And Thrombolysis strokE stuDy trial is a 2 × 2 quasi-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial that is evaluating in thrombolysis-eligible acute ischemic stroke patients whether: (1) low-dose (0·6 mg/kg body weight) intravenous alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage compared with standard-dose (0·9 mg/kg body weight) intravenous alteplase; and (2) early intensive blood pressure lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any intracerebral hemorrhage compared with guideline-recommended blood pressure control (systolic target <180 mmHg). To outline in detail the predetermined statistical analysis plan for the 'alteplase dose arm' of the study. All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with appropriate comparisons made between randomized groups. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. A statistical analysis plan was developed for the results of the alteplase dose arm of the study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. We have developed a predetermined statistical analysis plan for the ENhanced Control of Hypertension And Thrombolysis strokE stuDy alteplase dose arm which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

A systematic review of ultrasound-accelerated catheter-directed thrombolysis in the treatment of deep vein thrombosis.

PubMed

Shi, Yadong; Shi, Wanyin; Chen, Liang; Gu, Jianping

2018-04-01

To review the clinical evidence for ultrasound-accelerated catheter-directed thrombolysis (UACDT) using the EKOS system in the treatment of deep vein thrombosis (DVT) in terms of case selection, procedural outcomes, clinical outcomes and safety outcomes. A systematic literature search strategy was used to identify the use of the EKOS system in the treatment of DVT using the following electronic databases: MEDLINE, EMBASE, the Cochrane databases and the Web of Science. The references in the relevant literature were also screened. Our literature search identified a total of 16 unique clinical studies. Twelve of the sixteen studies were retrospective case series studies. To date, only one randomised controlled trial (RCT) is available. Overall, UACDT using the EKOS system was performed 548 times in 512 patients. Among all cases, 77-100% achieved substantial lysis (> 50%) based on the different definitions of the individual studies. This treatment modality appears to be safe, as there were no reported procedure-related pulmonary embolisms (PE) and only one procedure-related death was reported. Bleeding events were reported in 14 of the 16 studies, and 3.9% (20/512) of the cases of bleeding were considered major. During the follow-up, post-thrombotic syndrome was observed in 17.1% (20/117) of cases. UACDT using the EKOS system is an effective, safe and promising treatment modality for DVT, but the existing clinical evidence is inadequate to make UACDT using the EKOS system the first-line choice for DVT. Additional prospective large-sample RCTs with long-term follow-ups are warranted to define the role of UACDT using the EKOS system in the treatment of DVT.

Is there still a place for emergency department thrombolysis following the introduction of the amended Joint Royal Colleges Ambulance Liaison Committee criteria for thrombolysis?

PubMed

Castle, N R; Owen, R C; Hann, M

2007-12-01

To apply the current (2004) and the amended (2006) Joint Royal Colleges Ambulance Liaison Committee (JRCALC) criteria for paramedic initiated thrombolysis to all patients who received thrombolytic treatment in an emergency department (ED) to determine if the amendments increase the proportion suitable for paramedic initiated thrombolysis. Retrospective descriptive analysis. The ED clinical notes, ambulance clinical record and the first recorded ECG (ED or ambulance) of all patients thrombolysed in the ED during a 12 month period were reviewed against the previous JRCALC guidelines (2004) and the amended JRCALC guidelines (2006) for thrombolysis. Using the JRCALC guidelines (2004), 26 of the 147 patients (17.7%) were eligible for paramedic initiated thrombolysis. Using the JRCALC guidelines (2006), this increased to 41 (27.9%). This difference was statistically significant (McNemar's I2 test with 1 degree of freedom = 15.00; p<0.001). The change to the blood pressure, age and pulse rate parameters has increased the percentage eligible for paramedic initiated thrombolysis by 10.2% (95% confidence interval 4.6% to 15.8%). The amended JRCALC guidelines (2006) for paramedic initiated thrombolysis have successfully increased the proportion of patients suitable for prehospital thrombolysis by approximately 10%, although the ED retains an important role in the provision of prompt thrombolytic treatment for a proportion of patients.

High-Intensity Focused Ultrasound Therapy: an Overview for Radiologists

PubMed Central

Kim, Young-sun; Choi, Min Joo; Lim, Hyo Keun; Choi, Dongil

2008-01-01

High-intensity focused ultrasound therapy is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. This completely non-invasive technology has great potential for tumor ablation as well as hemostasis, thrombolysis and targeted drug/gene delivery. However, the application of this technology still has many drawbacks. It is expected that current obstacles to implementation will be resolved in the near future. In this review, we provide an overview of high-intensity focused ultrasound therapy from the basic physics to recent clinical studies with an interventional radiologist's perspective for the purpose of improving the general understanding of this cutting-edge technology as well as speculating on future developments. PMID:18682666

Single-transducer dual-frequency ultrasound generation to enhance acoustic cavitation.

PubMed

Liu, Hao-Li; Hsieh, Chao-Ming

2009-03-01

Dual- or multiple-frequency ultrasound stimulation is capable of effectively enhancing the acoustic cavitation effect over single-frequency ultrasound. Potential application of this sonoreactor design has been widely proposed such as on sonoluminescence, sonochemistry enhancement, and transdermal drug release enhancement. All currently available sonoreactor designs employed multiple piezoelectric transducers for generating single-frequency ultrasonic waves separately and then these waves were mixed and interfered in solutions. The purpose of this research is to propose a novel design of generating dual-frequency ultrasonic waves with single piezoelectric elements, thereby enhancing acoustic cavitation. Macroscopic bubbles were detected optically, and they were quantified at either a single-frequency or for different frequency combinations for determining their efficiency for enhancing acoustic cavitation. Visible bubbles were optically detected and hydrogen peroxide was measured to quantify acoustic cavitation. Test water samples with different gas concentrations and different power levels were used to determine the efficacy of enhancing acoustic cavitation of this design. The spectrum obtained from the backscattered signals was also recorded and examined to confirm the occurrence of stable cavitation. The results confirmed that single-element dual-frequency ultrasound stimulation can enhance acoustic cavitation. Under certain testing conditions, the generation of bubbles can be enhanced up to a level of five times higher than the generation of bubbles in single-frequency stimulation, and can increase the hydrogen peroxide production up to an increase of one fold. This design may serve as a useful alternative for future sonoreactor design owing to its simplicity to produce dual- or multiple-frequency ultrasound.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

PubMed

Yuan, Hai-Xia; Cao, Jia-Ying; Kong, Wen-Tao; Xia, Han-Sheng; Wang, Xi; Wang, Wen-Ping

2015-04-01

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Real-time 3-dimensional contrast-enhanced ultrasound in detecting hemorrhage of blunt renal trauma.

PubMed

Xu, Rui-Xue; Li, Ye-Kuo; Li, Ting; Wang, Sha-Sha; Yuan, Gui-Zhong; Zhou, Qun-Fang; Zheng, Hai-Rong; Yan, Fei

2013-10-01

The objective of this study is to evaluate the diagnostic value of real-time 3-dimensional contrast-enhanced ultrasound in the hemorrhage of blunt renal trauma. Eighteen healthy New Zealand white rabbits were randomly divided into 3 groups. Blunt renal trauma was performed on each group by using minitype striker. Ultrasonography, color Doppler flow imaging, and contrast-enhanced 2-dimensional and real-time 3-dimensional ultrasound were applied before and after the strike. The time to shock and blood pressure were subjected to statistical analysis. Then, a comparative study of ultrasound and pathology was carried out. All the struck kidneys were traumatic. In the ultrasonography, free fluid was found under the renal capsule. In the color Doppler flow imaging, active hemorrhage was not identified. In 2-dimensional contrast-enhanced ultrasound, active hemorrhage of the damaged kidney was characterized. Real-time 3-dimensional contrast-enhanced ultrasound showed a real-time and stereoscopic ongoing bleeding of the injured kidney. The wider the hemorrhage area in 4-dimensional contrast-enhanced ultrasound was, the faster the blood pressure decreased. Real-time 3-dimensional contrast-enhanced ultrasound is a promising noninvasive tool for stereoscopically and vividly detecting ongoing hemorrhage of blunt renal trauma in real time. © 2013.

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.

Reduced clot debris size using standing waves formed via high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Guo, Shifang; Du, Xuan; Wang, Xin; Lu, Shukuan; Shi, Aiwei; Xu, Shanshan; Bouakaz, Ayache; Wan, Mingxi

2017-09-01

The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic potential well which contributed to particle fragmentation.

Choices Regarding Thrombolysis Are Modified by the Way to Transfer the Messages.

PubMed

Gong, Jingjing; Zhang, Yan; Gao, Hongyan; Wei, Wei; Lv, Jing; Liu, Hongyun; Huang, Yonghua

2017-01-01

Although thrombolysis is the most effective medical treatment for acute ischemic stroke, many stroke patients eligible for thrombolysis miss this treatment as a result of delay or refusal by the patients and/or their proxies. To explore the influences of prognostic information for different intervals from stroke onset to the start of thrombolytic treatment (OTT) and other factors on the preferences of patients/proxies regarding thrombolytic therapy, a cross-sectional, discrete-choice experiment was performed between August 2013 and September 2014. A total of 613 Chinese inpatients or their immediate family members were consecutively recruited at the Department of Neurology. After random assignment to a negative-framing group or a positive-framing group, the subjects completed a series of surveys, including nine items about thrombolysis. Latent class analysis (LCA) was used to examine participants' preference paradigms for thrombolysis and to categorize the participants into different subgroups. Subsequently, regression analyses were conducted to explore predictors of categorization of the participants into each subgroup and to construct a thrombolytic decision-making model. LCA revealed an optimal 3-subgroup model including a consent to thrombolysis subgroup and objection to thrombolysis subgroups 1 and 2. Multiple regression analysis demonstrated that compared with assignment to the consent to thrombolysis subgroup, assignment to objection to thrombolysis subgroup 1 or 2 could be predicted by different factors. χ 2 tests indicated effects of framing and other factors on participants' choices regarding thrombolysis. Choices regarding thrombolysis were modified by not only prognostic information for different OTT intervals but also message framing, presentation format, and sociodemographic characteristics. To facilitate consent to thrombolysis, physicians should convey prognostic information to patients/proxies on the basis of patient OTT interval and should order

Choices Regarding Thrombolysis Are Modified by the Way to Transfer the Messages

PubMed Central

Gong, Jingjing; Zhang, Yan; Gao, Hongyan; Wei, Wei; Lv, Jing; Liu, Hongyun; Huang, Yonghua

2017-01-01

Although thrombolysis is the most effective medical treatment for acute ischemic stroke, many stroke patients eligible for thrombolysis miss this treatment as a result of delay or refusal by the patients and/or their proxies. To explore the influences of prognostic information for different intervals from stroke onset to the start of thrombolytic treatment (OTT) and other factors on the preferences of patients/proxies regarding thrombolytic therapy, a cross-sectional, discrete-choice experiment was performed between August 2013 and September 2014. A total of 613 Chinese inpatients or their immediate family members were consecutively recruited at the Department of Neurology. After random assignment to a negative-framing group or a positive-framing group, the subjects completed a series of surveys, including nine items about thrombolysis. Latent class analysis (LCA) was used to examine participants’ preference paradigms for thrombolysis and to categorize the participants into different subgroups. Subsequently, regression analyses were conducted to explore predictors of categorization of the participants into each subgroup and to construct a thrombolytic decision-making model. LCA revealed an optimal 3-subgroup model including a consent to thrombolysis subgroup and objection to thrombolysis subgroups 1 and 2. Multiple regression analysis demonstrated that compared with assignment to the consent to thrombolysis subgroup, assignment to objection to thrombolysis subgroup 1 or 2 could be predicted by different factors. χ2 tests indicated effects of framing and other factors on participants’ choices regarding thrombolysis. Choices regarding thrombolysis were modified by not only prognostic information for different OTT intervals but also message framing, presentation format, and sociodemographic characteristics. To facilitate consent to thrombolysis, physicians should convey prognostic information to patients/proxies on the basis of patient OTT interval and should

Ultrasound active nanoscaled lipid formulations for thrombus lysis.

PubMed

Becker, Andreas; Marxer, Elena; Brüssler, Jana; Hoormann, Anne Sophia; Kuhnt, Daniela; Bakowsky, Udo; Nimsky, Christopher

2011-04-01

In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Perfusion CT helps decision making for thrombolysis when there is no clear time of onset

PubMed Central

Hellier, K D; Hampton, J L; Guadagno, J V; Higgins, N P; Antoun, N M; Day, D J; Gillard, J H; Warburton, E A; Baron, J‐C

2006-01-01

Current guidelines on thrombolysis post stroke with recombinant tissue plasminogen activator (rt‐PA) exclude its use where time of onset is unknown, thus denying some patients potentially beneficial treatment. Contrast enhanced perfusion computed tomography (pCT) imaging can be used together with plain CT and information on clinical deficits to decide whether or not thrombolysis should be initiated even though the exact time of stroke onset is unknown. Based on the results of pCT and CT, rt‐PA was administered to two patients with unknown time of stroke onset; one of the patients also underwent suction thrombectomy. Results in both cases were excellent. PMID:16484659

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

Thrombolysis research--new objectives after a shift of accent.

PubMed

Maksimenko, Alexander V

2002-01-01

The methods of increasing the efficacy of thrombolysis under clinical and experimental conditions are have been discussed in the light of analysis of current tendencies in the investigation and development of thrombolytic and adjunctive therapy. Analysis of the data obtained in the search for novel plasminogen activators for thrombolytic enzyme therapy has shown a decrease and depletion of this search. The reserves for further increase in thrombolysis efficiency have been notified. Special attention is paid to the purposes, realms and problems of adjunctive therapy, which is a promising breakthrough area in the effort of increasing the efficacy of thrombolysis.

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

Experimental validation of a finite-difference model for the prediction of transcranial ultrasound fields based on CT images

NASA Astrophysics Data System (ADS)

Bouchoux, Guillaume; Bader, Kenneth B.; Korfhagen, Joseph J.; Raymond, Jason L.; Shivashankar, Ravishankar; Abruzzo, Todd A.; Holland, Christy K.

2012-12-01

The prevalence of stroke worldwide and the paucity of effective therapies have triggered interest in the use of transcranial ultrasound as an adjuvant to thrombolytic therapy. Previous studies have shown that 120 kHz ultrasound enhanced thrombolysis and allowed efficient penetration through the temporal bone. The objective of our study was to develop an accurate finite-difference model of acoustic propagation through the skull based on computed tomography (CT) images. The computational approach, which neglected shear waves, was compared with a simple analytical model including shear waves. Acoustic pressure fields from a two-element annular array (120 and 60 kHz) were acquired in vitro in four human skulls. Simulations were performed using registered CT scans and a source term determined by acoustic holography. Mean errors below 14% were found between simulated pressure fields and corresponding measurements. Intracranial peak pressures were systematically underestimated and reflections from the contralateral bone were overestimated. Determination of the acoustic impedance of the bone from the CT images was the likely source of error. High correlation between predictions and measurements (R2 = 0.93 and R2 = 0.88 for transmitted and reflected waves amplitude, respectively) demonstrated that this model is suitable for a quantitative estimation of acoustic fields generated during 40-200 kHz ultrasound-enhanced ischemic stroke treatment.

[Understanding the reasons behind the low utilization of thrombolysis in hyperacute ischemic stroke].

PubMed

Zhang, Xiaoxue; Zhang, Jingfen; Li, Ruiming; Cheng, Guojuan; Chen, Qiang

2016-03-22

The study aimed to analyze the influencing factors of thrombolysis therapy in acute ischemic stroke patients with onset time less than 4.5 hours. We consecutively prospectively screened acute ischemic stroke patients with onset time less than 4.5 hours from emergency department, outpatients and inpatients of neurology department, and image center in our hospital over a 31-month time period (April 2012-November 2014). The rate of thrombolysis and the reasons for not receiving thrombolysis were analyzed. A total of 538 patients who met the inclusion criteria were included (68.2% males, mean age 67±13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons for the patients not receiving thrombolysis included minor symptoms (172 cases, 39.6%), rapidly improving symptoms and high possibility of transient ischemic attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44, 10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years old (38, 8.8%). The thrombolysis rate within time window of acute ischemic stroke is remarkably higher than that of several years ago in China. The main reasons for not receiving thrombolysis are minor and rapidly improving symptoms, patients or families' refusal, in-hospital delay, elderly people with age over than 80 years old.

The Chinese Stroke Association scientific statement: intravenous thrombolysis in acute ischaemic stroke

PubMed Central

Dong, Qiang; Dong, Yi; Liu, Liping; Xu, Anding; Zhang, Yusheng; Zheng, Huaguang; Wang, Yongjun

2017-01-01

The most effective medical treatment for acute ischaemic stroke (AIS) is to offer intravenous thrombolysis during the ultra-early period of time after the onset. Even based on the Consensus of Chinese Experts on Intravenous Thrombolysis for AIS in 2012 and 2014 Chinese Guidelines on the Diagnosis and Treatment of AIS, the rate of thrombolysis for AIS in China remained around 2.4%, and the rate of intravenous tissue plasminogen activator usage was only about 1.6% in real world. The indication of thrombolysis for AIS has been expanded, and contraindications have been reduced with recently published studies. In order to facilitate the standardisation of treating AIS, improve the rate of thrombolysis and benefit patients who had a stroke, Chinese Stroke Association has organised and developed this scientific statement. PMID:28989804

Audit of thrombolysis initiated in an accident and emergency department.

PubMed Central

Nee, P A; Gray, A J; Martin, M A

1994-01-01

Early thrombolytic therapy after acute myocardial infarction is important in reducing mortality. To evaluate a system for reducing in-hospital delays to thrombolysis pain to needle and door to needle times to thrombolysis were audited in a major accident and emergency (A and E) department of a district general hospital and its coronary care unit (CCU), situated about 5 km away. Baseline performance over six months was assessed retrospectively from notes of 43 consecutive patients (group 1) transferred to the CCU before receiving thrombolysis. Subsequently, selected patients (23) were allowed to receive thrombolysis in the A and E department before transfer to the CCU. The agent was administered by medical staff in the department after receiving oral confirmation of myocardial infarction from the admitting medical officer in the CCU on receipt of fax transmission of the electrocardiogram. A second prospective audit during six months from the start of the new procedure established time intervals in 23 patients eligible to receive thrombolysis in the A and E department (group 2b) and 30 ineligible patients who received thrombolysis in the CCU (group 2a). The groups did not differ significantly in case mix, pre-hospital delay, or transfer time to the CCU. In group 2b door to needle time and pain to needle time were reduced significantly (geometric mean 38 min v 121 min (group 2a) and 128 min (group 1); 141 min v 237 min (group 2a) and 242 min (group 1) respectively, both p < 0.0001). The incidence of adverse effects was not significantly different. Nine deaths occurred (six in group 1, three in group 2b), an in-hospital mortality of 9.9%. Thrombolysis can be safely instituted in the A and E department in selected patients, significantly reducing delay to treatment. PMID:10136256

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

Efficacy of Lower-Extremity Venous Thrombolysis in the Setting of Congenital Absence or Atresia of the Inferior Vena Cava

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

Ganguli, Suvranu, E-mail: sganguli@partners.org; Kalva, Sanjeeva; Oklu, Rahmi

Purpose: A rare but described risk factor for deep venous thrombosis (DVT), predominately in the young, is congenital agenesis or atresia of the inferior vena cava (IVC). The optimal management for DVT in this subset of patients is unknown. We evaluated the efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) followed by systemic anticoagulation in the treatment of acute lower-extremity DVT in the setting of congenital IVC agenesis or atresia. Materials and Methods: Between November of 2005 and May of 2010, six patients (three women [average age 21 years]) were referred to our department with acute lower-extremity DVT and subsequently found tomore » have IVC agenesis or atresia on magnetic resonance imaging. A standardized technique for PCDT (the Angiojet Rheolytic Thrombectomy System followed by the EKOS Microsonic Accelerated Thrombolysis System) was used for all subjects. Successful thrombolysis was followed by systemic heparinization with transition to Coumadin or low molecular-weight heparin and compression stockings. Subjects were followed-up at 1, 3, and then every 6 months after the procedure with clinical assessment and bilateral lower-extremity venous ultrasound. Results: All PCDT procedures were technically successful. No venous stenting or angioplasty was performed. The average thrombolysis time was 28.6 h (range 12-72). Two patients experienced heparin-induced thrombocytopenia, and one patient developed a self-limited knee hemarthrosis, No patients were lost to follow-up. The average length of follow-up was 25.8 {+-} 20.2 months (range 3.8-54.8). No incidence of recurrent DVT was identified. There were no manifestations of postthrombotic syndrome. Conclusions: PCDT followed by systemic anticoagulation and the use of compression stockings appears to be safe and effective in relatively long-term follow-up treatment of patients who present with acute DVT and IVC agenesis or atresia.« less

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.

Mechanisms of thrombolysis acceleration by cavitation

NASA Astrophysics Data System (ADS)

Weiss, Hope; Selvaraj, Prashanth; Ahadi, Golnaz; Voie, Arne; Hoelscher, Thilo; Okita, Kohei; Matsumoto, Yoichiro; Szeri, Andrew

2012-11-01

Recent studies, in vitro and in vivo, have shown that High Intensity Focused Ultrasound (HIFU) accelerates thrombolysis, the dissolution of blood clots, for ischemic stroke. Although the mechanisms are not fully understood, cavitation is thought to play an important role in sonothrombolysis. The damage to a blood clot's fibrin fiber network from cavitation in a HIFU field is studied using two independent approaches for an embedded bubble. One method is extended to the more important scenario of a bubble outside a blood clot that collapses asymmetrically creating a jet towards the clot. There is significantly more damage potential from a bubble undergoing cavitation collapse outside the clot compared to a rapidly expanding bubble embedded within the clot structure. Also, the effects of the physical properties of skull bone when a HIFU wave propagates through it are examined by use of computer simulation. The dynamics of a test bubble placed at the focus is used in understanding of the pressure field. All other things being equal, the analysis suggests that skull thickness can alter the wave at the focus, which in turn can change the nature of cavitation bubble dynamics and the amount of energy available for clot damage. Now at MSOE.

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.

Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

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

Ferro, Carlo; Rossi, Umberto G., E-mail: urossi76@hotmail.com; Bovio, Giulio

2007-09-15

A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT.

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.

Noninvasive treatment of deep venous thrombosis using pulsed ultrasound cavitation therapy (histotripsy) in a porcine model.

PubMed

Maxwell, Adam D; Owens, Gabe; Gurm, Hitinder S; Ives, Kimberly; Myers, Daniel D; Xu, Zhen

2011-03-01

This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, high-intensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This is an in vivo feasibility study of histotripsy thrombolysis. Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm-diameter 1-MHz focused transducer was used for therapy. An 8-MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of five cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14 and 19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment. Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases and in 7 cases improved flow through the vein as measured by color Doppler. Vessel histology found denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed. The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Is it beneficial to increase the provision of thrombolysis?-- a discrete-event simulation model.

PubMed

Barton, M; McClean, S; Gillespie, J; Garg, L; Wilson, D; Fullerton, K

2012-07-01

Although Thrombolysis has been licensed in the UK since 2003, it is still administered only to a small percentage of eligible patients. We consider the impact of investing the impact of thrombolysis on important acute stroke services, and the effect on quality of life. The concept is illustrated using data from the Northern Ireland Stroke Service. Retrospective study. We first present results of survival analysis utilizing length of stay (LOS) for discharge destinations, based on data from the Belfast City Hospital (BCH). None of these patients actually received thrombolysis but from those who would have been eligible, we created two initial groups, the first representing a scenario where they received thrombolysis and the second comprising those who do not receive thrombolysis. On the basis of the survival analysis, we created several subgroups based on discharge destination. We then developed a discrete event simulation (DES) model, where each group is a patient pathway within the simulation. Coxian phase type distributions were used to model the group LOS. Various scenarios were explored focusing on cost-effectiveness across hospital, community and social services had thrombolysis been administered to these patients, and the possible improvement in quality of life, should the proportion of patients who are administered thrombolysis be increased. Our aim in simulating various scenarios for this historical group of patients is to assess what the cost-effectiveness of thrombolysis would have been under different scenarios; from this we can infer the likely cost-effectiveness of future policies. The cost of thrombolysis is offset by reduction in hospital, community rehabilitation and institutional care costs, with a corresponding improvement in quality of life. Our model suggests that provision of thrombolysis would produce moderate overall improvement to the service assuming current levels of funding.

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

Simulations of laser thrombolysis

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

Chapyak, E.J.; Godwin, R.P.

1999-03-01

The authors have shown that bubble expansion and collapse near the interface between two materials with modest property differences produces jet-like interpenetration of the two materials. The bubble dynamics at a water-viscous fluid interface is compared with that at the interface of water with a weak elastic-plastic material. The authors find that, despite rather similar behavior during bubble growth and the initial portion of bubble collapse, the terminal jetting behavior is quite different, even in direction. The elastic-plastic properties chosen realistically represent real and surrogate thrombus. Simulations using the elastic-plastic model quantitatively agree with laboratory thrombolysis mass removal experiments. Inmore » the earlier simulations of laboratory experiments, walls have been remote so as to not effect the dynamics. Here the authors present two-dimensional simulations of thrombolysis with water over elastic-plastic surrogate thrombus in a geometry representative of the clinical situation. The calculations include thin cylindrical elastic walls with properties and dimensions appropriate for arteries. The presence of these artery walls does not substantially change the interface jetting predicted in unconfined simulations.« less

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.

Potential and problems in ultrasound-responsive drug delivery systems

PubMed Central

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

2013-01-01

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

Spinal Epidural Hematoma After Thrombolysis for Deep Vein Thrombosis with Subsequent Pulmonary Thromboembolism: A Case Report

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

Han, Young-Min, E-mail: ymhan@chonbuk.ac.kr; Kwak, Ho-Sung; Jin, Gong-Young

2006-06-15

A 38-year-old male was initially admitted for left leg swelling. He was diagnosed as having deep vein thrombosis (DVT) in the left leg and a pulmonary thromboembolism by contrast-enhanced chest computed tomography (CT) with delayed lower extremity CT. The DVT was treated by thrombolysis and a venous stent. Four hours later, he complained of severe back pain and a sensation of separation of his body and lower extremities; he experienced paraplegia early in the morning of the following day. Magnetic resonance imaging showed a spinal epidural hematoma between T11 and L2, which decompressed following surgery. We, therefore, report a casemore » of a spinal epidural hematoma after thrombolysis in a case of DVT with a pulmonary thromboembolism.« less

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

Sonothrombolysis

PubMed Central

Bader, Kenneth B.; Bouchoux, Guillaume

2016-01-01

Thrombo-occlusive disease is a leading cause of morbidity and mortality. In this chapter, the use of ultrasound to accelerate clot breakdown alone or in combination with thrombolytic drugs will be reported. Primary thrombus formation during cardiovascular disease and standard treatment methods will be discussed. Mechanisms for ultrasound enhancement of thrombolysis, including thermal heating, radiation force, and cavitation, will be reviewed. Finally, in-vitro, in-vivo and clinical evidence of enhanced thrombolytic efficacy with ultrasound will be presented and discussed. PMID:26486347

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.

Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia.

PubMed

Chernyshev, Oleg Y; Garami, Zsolt; Calleja, Sergio; Song, Joon; Campbell, Morgan S; Noser, Elizabeth A; Shaltoni, Hashem; Chen, Chin-I; Iguchi, Yasuyuki; Grotta, James C; Alexandrov, Andrei V

2005-01-01

We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, > or =50% stenoses or thrombus in the symptomatic artery. One hundred and fifty patients (70 women, mean age 66+/-15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS > or =10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

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.

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.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

PubMed

Cortijo, E; García-Bermejo, P; Calleja, A I; Pérez-Fernández, S; Gómez, R; del Monte, J M; Reyes, J; Arenillas, J F

2014-03-01

Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis.

PubMed

Yang, Bin; Xu, Xiao-Dong; Gao, Peng; Yu, Ji-Xiang; Li, Yu; Zhu, Ai-Dong; Meng, Ran-Ran

2016-08-23

BACKGROUND There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). MATERIAL AND METHODS Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. RESULTS The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). CONCLUSIONS Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis.

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.

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.

Investigating Interactions between Ultrasound Stimulated Microbubbles and the Fibrin Network of Blood Clots

NASA Astrophysics Data System (ADS)

Acconcia, Christopher N.

The occlusion of blood vessels by thrombus is a major cause of mortality and morbidity in cardiovascular diseases such as deep vein thrombosis, myocardial infarction and ischemic stroke. In these contexts, prompt restoration of blood flow is of the utmost importance and is poorly addressed by current methods in many cases. For example, the treatment standard for ischemic stroke is administration of the thrombolytic agent tissue plasminogen activator, which is only minimally effective and has associated safety issues. There is, therefore, a need for the development of alternative recanalization strategies and amongst these, bubble mediated sonothrombolysis (thrombolysis by ultrasound) has emerged as a promising approach. Though it is well established that ultrasound stimulated microbubbles can potentiate the lysis of blood clots, the mechanisms are not well understood and this lack of understanding is a hindrance to the development of improved ultrasound exposure strategies. This thesis has revealed insights into the mechanisms of bubble mediated sonothrombolysis which can be used to guide the development of improved exposure strategies and contrast agents (i.e. bubble sizes) for sonothrombolysis treatments. The experimental approach involved fast frame optical imaging of ultrasound stimulated microbubbles interacting with clots, and two-photon fluorescence imaging of clots following ultrasound exposure. It was demonstrated that bubbles can penetrate fibrin clots, disrupt the fibrin network, generate patent tunnels, enhance the transport of fluid into the clot and induce clot boundary displacements. Furthermore, the occurrence and extent of these therapeutically relevant effects were shown to be highly dependent on pulse length and bubble size: longer pulses and larger bubbles were associated with greater disruption of fibrin networks and greater fluid transport distances. Finally, it was shown that bubbles can induce the ejection of erythrocytes from blood clots

Extensive Mobile Thrombus of the Internal Carotid Discovered After Intravenous Thrombolysis

PubMed Central

Fugate, Jennifer E.; Hocker, Sara E.

2016-01-01

This case report describes a rare presentation of ischemic stroke secondary to an extensive internal carotid artery thrombus, subsequent therapeutic dilemma, and clinical management. A 58-year-old man was administered intravenous (IV) thrombolysis for right middle cerebral artery territory ischemic stroke symptoms. A computed tomography angiogram of the head and neck following thrombolysis showed a longitudinally extensive internal carotid artery thrombus originating at the region of high-grade calcific stenosis. Mechanical embolectomy was deferred because of risk of clot dislodgement and mild neurological symptoms. Recumbency and hemodynamic augmentation were used acutely to support cerebral perfusion. Anticoagulation was started 24 hours after thrombolysis. Carotid endarterectomy was completed successfully within 1 week of presentation. Clinical outcome was satisfactory with discharge modified Rankin Scale score 0. A longitudinally extensive carotid artery thrombus poses a risk of dislodgement and hemispheric stroke. Optimal management in these cases is not known with certainty. In our case, IV thrombolysis, hemodynamic augmentation, delayed anticoagulation, and carotid endarterectomy resulted in a favorable clinical outcome. PMID:28400904

Spontaneous sternocleidomastoid muscle hematoma following thrombolysis for acute ischemic stroke.

PubMed

Giannantoni, Nadia Mariagrazia; Della Marca, Giacomo; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Frisullo, Giovanni

2014-06-15

Spontaneous or traumatic bleeding is a common complication of systemic thrombolysis in patients with acute ischemic stroke. We report the case of an 83 y.o. woman with right facio-brachio-crural hemiparesis, left deviation of the head and aphasia who developed, after thrombolytic therapy, a spontaneous sternocleidomastoid muscle hematoma that regressed few days later. To our knowledge, this is the first case reported in the literature of asymptomatic and spontaneous skeletal muscle hematoma following thrombolysis for the treatment of acute ischemic stroke. The occurrence of lateral cervical tuberculosis lymphadenitis ipsilateral to sternocleidomastoid muscle hematoma may suggest a causal relationship between local chronic inflammation of active mycobacterial infection and thrombolysis-related extravasation. This case should suggest caution in thrombolytic treatment in patients with chronic immune dysregulation and vascular inflammation such as extra-pulmonary tuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Catheter-Directed Thrombolysis of Lower Limb Thrombosis

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

Pianta, Marcus J.; Thomson, Kenneth R., E-mail: k.thomson@alfred.org.au

2011-02-15

Late complications of thrombosis of the deep veins in the region between the popliteal vein termination and the confluence of the common iliac veins and inferior vena cava (suprapopliteal deep-vein thrombosis) are common and often unrecognized by those responsible for the initial management. Pharmacomechanical-assisted clearance of the thrombus at the time of first presentation provides the best opportunity for complete recovery with preservation of normal venous valve function and avoidance of recurrent deep-vein thrombosis and postthrombotic syndrome. Recent interventional radiology methods provide for rapid and complete thrombolysis even in some patients in whom thrombolysis was previously considered contraindicated. This reviewmore » describes the methods, safety, and efficacy of acute interventional treatment of suprapopliteal deep-vein thrombosis.« less

Stroke thrombolysis: save a minute, save a day.

PubMed

Meretoja, Atte; Keshtkaran, Mahsa; Saver, Jeffrey L; Tatlisumak, Turgut; Parsons, Mark W; Kaste, Markku; Davis, Stephen M; Donnan, Geoffrey A; Churilov, Leonid

2014-04-01

Stroke thrombolysis is highly time-critical, but data on long-term effects of small reductions in treatment delays have not been available. Our objective was to quantify patient lifetime benefits gained from faster treatment. Observational prospective data of consecutive stroke patients treated with intravenous thrombolysis in Australian and Finnish centers (1998-2011; n=2258) provided distributions of age, sex, stroke severity, onset-to-treatment times, and 3-month modified Rankin Scale in daily clinical practice. Treatment effects derived from a pooled analysis of thrombolysis trials were used to model the shift in 3-month modified Rankin Scale distributions with reducing treatment delays, from which we derived the expected lifetime and level of long-term disability with faster treatment. Each minute of onset-to-treatment time saved granted on average 1.8 days of extra healthy life (95% prediction interval, 0.9-2.7). Benefit was observed in all groups: each minute provided 0.6 day in old severe (age, 80 years; National Institutes of Health Stroke Scale [NIHSS] score, 20) patients, 0.9 day in old mild (age, 80 years; NIHSS score, 4) patients, 2.7 days in young mild (age, 50 years; NIHSS score, 4) patients, and 3.5 days in young severe (age, 50 years; NIHSS score, 20) patients. Women gained slightly more than men over their longer lifetimes. In the whole cohort, each 15 minute decrease in treatment delay provided an average equivalent of 1 month of additional disability-free life. Realistically achievable small reductions in stroke thrombolysis delays would result in significant and robust average health benefits over patients' lifetimes. The awareness of concrete importance of speed could promote practice change.

How is stroke thrombolysis portrayed in UK national and London local newspapers? A review and critical discourse analysis.

PubMed

Cluckie, Gillian; Rudd, Anthony G; McKevitt, Christopher

2012-05-01

thrombolysis for stroke has been licensed in the UK since 2007 and needs to be administered within 4.5 h. Given this time critical factor, the media may have an important role in public awareness. this review aimed to find out how stroke thrombolysis was reported in UK national and London local newspapers and how treatment risks and benefits were communicated. Newspapers published between 1 January 2007 and 31 March 2010 were searched for articles on thrombolysis. Fifty-six articles were included and dispositive analysis, a qualitative analysis method, was used to identify themes. four main themes were identified: inaccurate description of thrombolysis, stroke clinicians' involvement, presentation of risks and benefits and patient stories. Inaccuracies included the presentation of thrombolysis as a treatment for transient ischaemic attack. Clinicians were quoted to suggest that thrombolysis produced complete recovery but were not reported to discuss risks or broader stroke management. The articles reported little or no risks of treatment. Patients' stories were used to reinforce that thrombolysis produces full recovery. this review found that newspaper media provides the public with inaccurate perspectives on thrombolysis. Clinicians may wish to check press articles prior to publishing and to consider the impact of reporting thrombolysis as a treatment which produces complete recovery.

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

Body temperature and outcome after stroke thrombolysis.

PubMed

Ernon, L; Schrooten, M; Thijs, V

2006-07-01

We studied whether baseline body temperature and temperature increases after stroke adversely affect outcome after thrombolysis with intravenous tissue plasminogen activator (IV tPA). The evolution of body temperature in the first 24 h after treatment with IV tPA was described by calculating the area under the curve of the temperature over time plot relative to temperature at admission (AUCBL) and relative to a standard value of 37 degrees C (AUC37). Temperature parameters were related to functional outcome. The median baseline National Institutes of Health Stroke Scale of 100 consecutive patients was 16 (interquartile range 11-21) and 34 patients had a favourable response to tPA. Patients with an unfavourable outcome had a more important temperature elevation than patients who had a favourable outcome after tPA (+1 degrees C vs +0.6 degrees C, P=0.02), despite similar baseline T and had a higher AUCBL (9.79 vs 5.36, P=0.027) and more frequently showed hyperthermia relative to baseline (82% vs 56%, P=0.011). After adjustment for baseline characteristics, the presence of hyperthermia relative to baseline was associated with a reduced odds of good outcome after thrombolysis (OR 0.34, 95% CI 0.10-0.95, P=0.040). Hyperthermia relative to baseline temperature in the 24 h after intravenous thrombolysis is associated with an unfavourable outcome.

Floating arterial thrombus related stroke treated by intravenous thrombolysis.

PubMed

Vanacker, P; Cordier, M; Janbieh, J; Federau, C; Michel, P

2014-01-01

The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be

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.

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech.

PubMed

Furlanis, Giovanni; Ridolfi, Mariana; Polverino, Paola; Menichelli, Alina; Caruso, Paola; Naccarato, Marcello; Sartori, Arianna; Torelli, Lucio; Pesavento, Valentina; Manganotti, Paolo

2018-07-01

Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data.

PubMed

Zinkstok, Sanne M; Vergouwen, Mervyn D I; Engelter, Stefan T; Lyrer, Philippe A; Bonati, Leo H; Arnold, Marcel; Mattle, Heinrich P; Fischer, Urs; Sarikaya, Hakan; Baumgartner, Ralf W; Georgiadis, Dimitrios; Odier, Céline; Michel, Patrik; Putaala, Jukka; Griebe, Martin; Wahlgren, Nils; Ahmed, Niaz; van Geloven, Nan; de Haan, Rob J; Nederkoorn, Paul J

2011-09-01

The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

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.

Thrombolysis for acute ischaemic stroke with alteplase in an Asian population: results of the multicenter, multinational Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW).

PubMed

Rha, Joung-Ho; Shrivastava, Vasantha Padma; Wang, Yongjun; Lee, Kim En; Ahmed, Niaz; Bluhmki, Erich; Hermansson, Karin; Wahlgren, Nils

2014-10-01

Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. To evaluate the efficacy and safety of intravenous alteplase (0·9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score ≥4 or death within the first 24 h) intracerebral haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month follow-up. The secondary outcome was functional independence (modified Rankin Scale score 0-2) at three-months. Results were compared with those from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled results of patients (n = 415) who received intravenous alteplase (0·9 mg/kg) zero- to three-hours from onset of stroke symptoms in four randomized controlled trials (National Institute of Neurological Disorders and Stroke A and B, Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke, and European Cooperative Acute Stroke Study II). Results are presented as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs. Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13

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...

A qualitative study of paramedics' attitudes to providing prehospital thrombolysis

PubMed Central

Price, L; Keeling, P; Brown, G; Hughes, D; Barton, A

2005-01-01

Method: In-depth interviews with 20 paramedics were recorded and transcribed and analysed for emergent themes using the constant comparative method. Results: Although there was a will to provide PHT because of its benefits to patients, its associated risks, aspects of pay and working conditions, and certain organisational factors undermined the willingness of some paramedics to administer thrombolysis. The eight minute response time standard is a competing imperative which can delay thrombolysis. Conclusions: A minority of paramedics are likely to be unwilling to deliver PHT unless countervailing imperatives are addressed. PMID:16189044

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

PubMed Central

Yang, Hung-Wei; Hua, Mu-Yi; Lin, Kun-Ju; Wey, Shiaw-Pyng; Tsai, Rung-Ywan; Wu, Siao-Yun; Lu, Yi-Ching; Liu, Hao-Li; Wu, Tony; Ma, Yunn-Hwa

2012-01-01

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases. PMID:23055728

Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?

PubMed

Balaz, P; Wohlfahrt, P; Rokosny, S; Maly, S; Bjorck, M

2016-09-01

Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 ± 9% and 32 ± 9% in patients with a venous allograft bypass and 46 ± 10% and 22 ± 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 ± 7%, 72 ± 8% and 63 ± 9%, and in the autologous group 91 ± 6%, 76 ± 9%, and 65 ± 13%, with no difference between groups (p = .69). Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

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 online benchmarking increase rates of thrombolysis? Data from the Austrian stroke unit registry.

PubMed

Ferrari, Julia; Seyfang, Leonhard; Lang, Wilfried

2013-09-01

Despite its widespread availability and known safety and efficacy, a therapy with intravenous thrombolysis is still undergiven. We aimed to identify whether nationwide quality projects--like the stroke registry in Austria--as well as online benchmarking and predefined target values can increase rates of thrombolysis. Therefore, we assessed 6,394 out of 48,462 patients with ischemic stroke from the Austrian stroke registry (study period from March 2003 to December 2011) who had undergone thrombolysis treatment. We defined lower level and target values as quality parameters and evaluated whether or not these parameters could be achieved in the past years. We were able to show that rates of thrombolysis in Austria increased from 4.9% in 2003 to 18.3% in 2011. In a multivariate regression model, the main impact seen was the increase over the years [the OR ranges from 0.47 (95% CI 0.32-0.68) in 2003 to 2.51 (95% CI 2.20-2.87) in 2011). The predefined lower and target levels of thrombolysis were achieved at the majority of participating centers: in 2011 the lower value of 5% was achieved at all stroke units, and the target value of 15% was observed at 21 of 34 stroke units. We conclude that online benchmarking and the concept of defining target values as a tool for nationwide acute stroke care appeared to result in an increase in the rate of thrombolysis over the last few years while the variability between the stroke units has not yet been reduced.

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.

Current status of intravenous thrombolysis for acute ischemic stroke in Asia.

PubMed

Sharma, Vijay K; Ng, Kay W P; Venketasubramanian, Narayanaswamy; Saqqur, Maher; Teoh, Hock L; Kaul, Subash; Srivastava, Padma M V; Sergentanis, Theodoris; Suwanwela, Nijasri; Nguyen, Thang H; Lawrence Wong, K S; Chan, Bernard P L

2011-12-01

Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0.6 mg/kg body weight; max 60 mg) comparable to standard dose (0.9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Patient Selection for Drip and Ship Thrombolysis in Acute Ischemic Stroke

PubMed Central

Lyerly, Michael J.; Albright, Karen C.; Boehme, Amelia K.; Shahripour, Reza Bavarsad; Donnelly, John P.; Houston, James T.; Rawal, Pawan V.; Kapoor, Niren; Alvi, Muhammad; Sisson, April; Alexandrov, Anne W.; Alexandrov, Andrei V.

2017-01-01

Objectives The drip and ship model is a method used to deliver thrombolysis to acute stroke patients in facilities lacking onsite neurology coverage. We sought to determine whether our drip and ship population differs from patients treated directly at our stroke center (direct presenters). Methods We retrospectively reviewed consecutive patients who received thrombolysis at an outside facility with subsequent transfer to our center between 2009 and 2011. Patients received thrombolysis after telephone consultation with a stroke specialist. We examined demographics, vascular risk factors, laboratory values, and stroke severity in drip and ship patients compared with direct presenters. Results Ninety-six patients were identified who received thrombolysis by drip and ship compared with 212 direct presenters. The two groups did not differ with respect to sex, ethnicity, vascular risk factors, or admission glucose. The odds ratio (OR) of arriving at our hospital as a drip and ship for someone 80 years or older was 0.31 (95% confidence interval [CI] 0.15–0.61, P < 0.001). Only 21% of drip and ship patients were black versus 38% of direct presenters (OR 0.434, 95% CI 0.25–0.76, P = 0.004). Even after stratifying by age (<80 vs ≥80), a smaller proportion of drip and ship patients were black (OR 0.44, 95% CI 0.24–0.81, P = 0.008). Furthermore, we found that fewer black patients with severe strokes arrived by drip and ship (OR 0.33, 95% CI 0.11–0.98, P = 0.0028). Conclusions Our study showed that a smaller proportion of blacks and older adults arrived at our center by the drip and ship model. This may reflect differences in how patients are selected for thrombolysis and transfer to a higher level of care. PMID:26192934

Patient Selection for Drip and Ship Thrombolysis in Acute Ischemic Stroke.

PubMed

Lyerly, Michael J; Albright, Karen C; Boehme, Amelia K; Shahripour, Reza Bavarsad; Donnelly, John P; Houston, James T; Rawal, Pawan V; Kapoor, Niren; Alvi, Muhammad; Sisson, April; Alexandrov, Anne W; Alexandrov, Andrei V

2015-07-01

The drip and ship model is a method used to deliver thrombolysis to acute stroke patients in facilities lacking onsite neurology coverage. We sought to determine whether our drip and ship population differs from patients treated directly at our stroke center (direct presenters). We retrospectively reviewed consecutive patients who received thrombolysis at an outside facility with subsequent transfer to our center between 2009 and 2011. Patients received thrombolysis after telephone consultation with a stroke specialist. We examined demographics, vascular risk factors, laboratory values, and stroke severity in drip and ship patients compared with direct presenters. Ninety-six patients were identified who received thrombolysis by drip and ship compared with 212 direct presenters. The two groups did not differ with respect to sex, ethnicity, vascular risk factors, or admission glucose. The odds ratio (OR) of arriving at our hospital as a drip and ship for someone 80 years or older was 0.31 (95% confidence interval [CI] 0.15-0.61, P < 0.001). Only 21% of drip and ship patients were black versus 38% of direct presenters (OR 0.434, 95% CI 0.25-0.76, P = 0.004). Even after stratifying by age (<80 vs ≥80), a smaller proportion of drip and ship patients were black (OR 0.44, 95% CI 0.24-0.81, P = 0.008). Furthermore, we found that fewer black patients with severe strokes arrived by drip and ship (OR 0.33, 95% CI 0.11-0.98, P = 0.0028). Our study showed that a smaller proportion of blacks and older adults arrived at our center by the drip and ship model. This may reflect differences in how patients are selected for thrombolysis and transfer to a higher level of care.

Relationship of Early Spontaneous Type V Blood Pressure Fluctuation after Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis

PubMed Central

Zuo, Lian; Wan, Ting; Xu, Xiahong; Liu, Feifeng; Li, Changsong; Li, Ying; Zhang, Yue; Zhang, Jing; Bao, Huan; Li, Gang

2016-01-01

We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients’ prognosis; however, this needs to be confirmed in future trials. PMID:27278121

STARTING-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis for Stroke.

PubMed

Cappellari, Manuel; Turcato, Gianni; Forlivesi, Stefano; Zivelonghi, Cecilia; Bovi, Paolo; Bonetti, Bruno; Toni, Danilo

2018-02-01

Symptomatic intracerebral hemorrhage (sICH) is a rare but the most feared complication of intravenous thrombolysis for ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients included in the multicenter SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register). All patients registered in the SITS-ISTR by 179 Italian centers between May 2001 and March 2016 were originally included. The main outcome measure was sICH per the European Cooperative Acute Stroke Study II definition (any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline or death <7 days). On the basis of multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver-operating characteristic curve and calibration of risk prediction model by using the Hosmer-Lemeshow test. A total of 15 949 patients with complete data for generating the nomogram was randomly dichotomized into training (3/4; n=12 030) and test (1/4; n=3919) sets. After multivariate logistic regression, 10 variables remained independent predictors of sICH to compose the STARTING-SICH (systolic blood pressure, age, onset-to-treatment time for thrombolysis, National Institutes of Health Stroke Scale score, glucose, aspirin alone, aspirin plus clopidogrel, anticoagulant with INR ≤1.7, current infarction sign, hyperdense artery sign) nomogram. The area under the receiver-operating characteristic curve of STARTING-SICH was 0.739. Calibration was good ( P =0.327 for the Hosmer-Lemeshow test). The STARTING-SICH is the first nomogram developed and validated in a large SITS-ISTR cohort for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients. © 2018 American Heart Association, Inc.

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...

Endocapsular hematoma: a rare form of ocular hemorrhage after thrombolysis with streptokinase.

PubMed

Dhawan, Bodhraj; Soni, Rhibhu; Singh, Rajbir; Vig, Vipan

2014-08-01

Endocapsular hematoma has previously been described as a cataract surgery complication more commonly observed in eyes receiving a combined cataract and glaucoma surgery. However, it can also be a rare form of ocular bleed following thrombolysis with streptokinase. A 65-year-old diabetic male presented to us with complain of sudden painless diminution of vision in his left eye, which he developed while he was being thrombolysed with streptokinase administered intravenously for an episode of acute myocardial infarct. On examination, left eye was pseudophakic with collection of blood in the capsular bag (Endocapsular hematoma). Endocapsular hematoma can be a rare form of ocular bleeding complicated by thrombolysis. Reporting this case becomes more relevant in the present era with increasing number of patients suffering from ischemic heart disease and likely to undergo thrombolysis.

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

Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

PubMed

Asdaghi, Negar; Wang, Kefeng; Ciliberti-Vargas, Maria A; Gutierrez, Carolina Marinovic; Koch, Sebastian; Gardener, Hannah; Dong, Chuanhui; Rose, David Z; Garcia, Enid J; Burgin, W Scott; Zevallos, Juan Carlos; Rundek, Tatjana; Sacco, Ralph L; Romano, Jose G

2018-03-01

Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). Among 73 712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ≤5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0-2 hours versus ≥3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95) were

Renal Infarction Caused by Spontaneous Renal Artery Dissection: Treatment with Catheter-Directed Thrombolysis and Stenting

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

Jeon, Yong Sun, E-mail: radjeon@korea.com; Cho, Soon Gu; Hong, Ki Cheon

2009-03-15

Spontaneous renal artery dissection (SRAD) is rare and presents a diagnostic and therapeutic challenge. We report a case of a 36-year-old man who had an SRAD-complicated renal infarction. The patient experienced severe unilateral flank pain. Enhanced abdominal computed axial tomography scan showed renal infarction, and urinalysis showed no hematuria. Selective renal angiography was essential to evaluate the extent of dissection and suitability for repair. The patient was treated with catheter-directed thrombolysis and frenal artery stenting.

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

Dimerized plasmin fragment D as a potential biomarker to predict successful catheter-directed thrombolysis therapy in acute deep vein thrombosis.

PubMed

Luo, Chien-Ming; Wu, I-Hui; Chan, Chih-Yang; Chen, Yih-Sharng; Yang, Wei-Shiung; Wang, Shoei-Shen

2015-10-01

The value of dimerized plasmin fragment D in the clinical monitoring during the catheter-directed thrombolysis in patients with acute deep vein thrombosis is not known. Dimerized plasmin fragment D levels in 24 patients with acute deep vein thrombosis undergoing catheter-directed thrombolysis were prospectively evaluated. The plasma dimerized plasmin fragment D level was measured serially before and at every 12 h during catheter-directed thrombolysis for 24 h. Technical success was defined as restoration of patency and flow with less than 50% residual thrombus by surveillance rotational venography. Technical success was achieved in 79.2% (19 of 24) of the treated limbs after catheter-directed thrombolysis. In univariate analysis, there was significant elevation of the dimerized plasmin fragment D at 12th h after starting the catheter-directed thrombolysis (P < 0.05) in patients with less than 50% residual thrombus stenosis. The optimal cut-off value of dimerized plasmin fragment D to predict successful catheter-directed thrombolysis was determined as 18.4 µg/ml at the 12th h after starting the catheter-directed thrombolysis with sensitivity 0.8 and specificity 0.8 (P = 0.03). It was further validated in multivariate logistic regression analysis (odds ratio: 14.38; 95% CI: 1.22-169.20; P = 0.03). Catheter-directed thrombolysis is safe and effective for restoration of blood flow in patients with acute deep vein thrombosis. Dimerized plasmin fragment D value greater than 18.4 µg/ml at the 12th h after starting catheter-directed thrombolysis had a high predictive rate of greater than 50% lysis at the end of catheter-directed thrombolysis. © The Author(s) 2014.

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.

Cost-effectiveness of optimizing acute stroke care services for thrombolysis.

PubMed

Penaloza-Ramos, Maria Cristina; Sheppard, James P; Jowett, Sue; Barton, Pelham; Mant, Jonathan; Quinn, Tom; Mellor, Ruth M; Sims, Don; Sandler, David; McManus, Richard J

2014-02-01

Thrombolysis in acute stroke is effective up to 4.5 hours after symptom onset but relies on early recognition, prompt arrival in hospital, and timely brain scanning. This study aimed to establish the cost-effectiveness of increasing thrombolysis rates through a series of hypothetical change strategies designed to optimize the acute care pathway for stroke. A decision-tree model was constructed, which relates the acute management of patients with suspected stroke from symptom onset to outcome. Current practice was modeled and compared with 7 change strategies designed to facilitate wider eligibility for thrombolysis. The model basecase consisted of data from consenting patients following the acute stroke pathway recruited in participating hospitals with data on effectiveness of treatment and costs from published sources. All change strategies were cost saving while increasing quality-adjusted life years gained. Using realistic estimates of effectiveness, the change strategy with the largest potential benefit was that of better recording of onset time, which resulted in 3.3 additional quality-adjusted life years and a cost saving of US $46,000 per 100,000 population. All strategies increased the number of thrombolysed patients and the number requiring urgent brain imaging (by 9% to 21% dependent on the scenario). Assuming a willingness-to-pay of US $30,000 per quality-adjusted life year gained, the potential budget available to deliver the interventions in each strategy ranged from US $50,000 to US $144,000. These results suggest that any strategy that increases thrombolysis rates will result in cost savings and improved patient quality of life. Healthcare commissioners could consider this model when planning improvements in stroke care.

[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.

Effects of lipoprotein(a) on thrombolysis.

PubMed

von Hodenberg, E; Pestel, E; Kreuzer, J; Freitag, M; Bode, C

1994-01-01

Lipoprotein(a) (Lp(a)) and plasminogen share a high degree of structural homology. Therefore it has been suggested that elevated levels of Lp(a) may inhibit the profibrinolytic activity at the cell surface and increase the risk of thrombosis by competitive inhibition of plasminogen. In the present study we evaluated whether high levels of Lp(a) affect thrombolytic therapy in patients with acute myocardial infarction. Forty-one patients with acute myocardial infarction were treated with a combination of recombinant tissue-type plasminogen activator and human single-chain urokinase-type plasminogen activator. Coronary patency was assessed angiographically 90 min after initiation of treatment. Thrombolysis was successful in 30 and unsuccessful in 11 patients. Patients with high Lp(a) levels (> 25 mg/dl) (n = 9) responded equally well to thrombolytic therapy (8 of 9, patency 89%) as did patients with normal or low levels of Lp(a) (22 of 32, patency 70%, difference P > 0.1). The results demonstrate that high levels of Lp(a) do not influence thrombolysis in patients with acute myocardial infarction when low-dose pharmacologic concentrations of recombinant tissue-type plasminogen activator and human single chain urokinase-type plasminogen activator are applied in combination.

[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 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.

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.

Mechanical Recanalization following i.v. Thrombolysis: A Retrospective Analysis regarding Secondary Hemorrhagic Infarctions and Parenchymal Hematomas

PubMed Central

Höltje, J.; Bonk, F.; Anstadt, A.; Terborg, C.; Pohlmann, C.; Urban, P. P.; Brüning, R.

2015-01-01

Introduction. In acute stroke by occlusion of the proximal medial cerebral artery (MCA) or the distal internal carotid artery, intravenous thrombolysis is an established treatment. Another option is mechanical recanalization. It remains unclear if the combination of both methods poses an additional bleeding risk. The aim of this retrospective analysis is to determine the proportion of hemorrhagic infarctions and parenchymal hematomas. Methods. Inclusion criteria were an occlusion of the carotid T or proximal MCA treated with full dose thrombolysis and mechanical recanalization. 31 patients were selected. Devices used were Trevo, Penumbra Aspiration system, Penumbra 3D Retriever, and Revive. The initial control by computed tomography was carried out with a mean delay to intervention of 10.9 hours (SD: 8.5 hours). Results. A slight hemorrhagic infarction (HI1) was observed in 2/31 patients, and a more severe HI2 occurred in two cases. A smaller parenchymal hematoma (PH1) was not seen and a space-occupying PH2 was seen in 2/31 cases. There was no significant difference in the probability of intracranial bleeding after successful (thrombolysis in cerebral infarctions 2b and 3) or unsuccessful recanalization. Conclusion. The proportion of intracranial bleeding using mechanical recanalization following intravenous thrombolysis appears comparable with reports using thrombolysis alone. PMID:26640710

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.

Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

NASA Astrophysics Data System (ADS)

Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

2005-03-01

Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.

Interactions between individual ultrasound-stimulated microbubbles and fibrin clots.

PubMed

Acconcia, Christopher; Leung, Ben Y C; Manjunath, Anoop; Goertz, David E

2014-09-01

The use of ultrasound-stimulated microbubbles (USMBs) to promote thrombolysis is well established, but there remains considerable uncertainty about the mechanisms of this process. Here we examine the microscale interactions between individual USMBs and fibrin clots as a function of bubble size, exposure conditions and clot type. Microbubbles (n = 185) were placed adjacent to clot boundaries ("coarse" or "fine") using optical tweezers and exposed to 1-MHz ultrasound as a function of pressure (0.1-0.39 MPa). High-speed (10 kfps) imaging was employed, and clots were subsequently assessed with 2-photon microscopy. For fine clots, 46% of bubbles "embedded" within 10 μm of the clot boundary at pressures of 0.1 and 0.2 MPa, whereas at 0.39 MPa, 53% of bubbles penetrated and transited into the clots with an incidence inversely related to their diameter. A substantial fraction of penetrating bubbles induced fibrin network damage and promoted the uptake of nanobeads. In coarse clots, penetration occurred more readily and at lower pressures than in fine clots. The results therefore provide direct evidence of therapeutically relevant effects of USMBs and indicate their dependence on size, exposure conditions and clot properties. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. 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

Thrombolysis in Acute Ischemic Stroke: A Simulation Study to Improve Pre- and in-Hospital Delays in Community Hospitals

PubMed Central

Lahr, Maarten M. H.; van der Zee, Durk-Jouke; Vroomen, Patrick C. A. J.; Luijckx, Gert-Jan; Buskens, Erik

2013-01-01

Background Various studies demonstrate better patient outcome and higher thrombolysis rates achieved by centralized stroke care compared to decentralized care, i.e. community hospitals. It remains largely unclear how to improve thrombolysis rate in decentralized care. The aim of this simulation study was to assess the impact of previously identified success factors in a central model on thrombolysis rates and patient outcome when implemented for a decentral model. Methods Based on a prospectively collected dataset of 1084 ischemic stroke patients, simulation was used to replicate current practice and estimate the effect of re-organizing decentralized stroke care to resemble a centralized model. Factors simulated included symptom onset call to help, emergency medical services transportation, and in-hospital diagnostic workup delays. Primary outcome was proportion of patients treated with thrombolysis; secondary endpoints were good functional outcome at 90 days, Onset-Treatment-Time (OTT), and OTT intervals, respectively. Results Combining all factors might increase thrombolysis rate by 7.9%, of which 6.6% ascribed to pre-hospital and 1.3% to in-hospital factors. Good functional outcome increased by 11.4%, 8.7% ascribed to pre-hospital and 2.7% to in-hospital factors. The OTT decreased 17 minutes, 7 minutes ascribed to pre-hospital and 10 minutes to in-hospital factors. An increase was observed in the proportion thrombolyzed within 1.5 hours; increasing by 14.1%, of which 5.6% ascribed to pre-hospital and 8.5% to in-hospital factors. Conclusions Simulation technique may target opportunities for improving thrombolysis rates in acute stroke. Pre-hospital factors proved to be the most promising for improving thrombolysis rates in an implementation study. PMID:24260151

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.

Thrombolysis based on magnetically-controlled surface-functionalized Fe3O4 nanoparticle

PubMed Central

Chang, Ming; Lin, Yu-Hao; Gabayno, Jacque Lynn; Li, Qian; Liu, Xiaojun

2017-01-01

ABSTRACT In this study, the control of magnetic fields to manipulate surface-functionalized Fe3O4 nanoparticles by urokinase coating is investigated for thrombolysis in a microfluidic channel. The urokinase-coated Fe3O4 nanoparticles are characterized using particle size distribution, zeta potential measurement and spectroscopic data. Thrombolytic ratio tests reveal that the efficiency for thrombus cleaning is significantly improved when using magnetically-controlled urokinase-coated Fe3O4 nanoparticles than pure urokinase solution. The average increase in the rate of thrombolysis with the use of urokinase-coated Fe3O4 nanoparticles is about 50%. In vitro thrombolysis test in a microfluidic channel using the coated nanoparticles shows nearly complete removal of thrombus, a result that can be attributed to the clot busting effect of the urokinase as it inhibits the possible formation of blood bolus during the magnetically-activated microablation process. The experiment further demonstrates that a thrombus mass of 10.32 mg in the microchannel is fully removed in about 180 s. PMID:27689864

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...

Risks of atrial fibrillation and death at discharge after thrombolysis in stroke patients: Northumbrian Sentinel Stroke Audit, 2013-2015.

PubMed

Shiue, I

2017-02-01

The aim of this study was to examine risks of atrial fibrillation and death at discharge in stroke patients treated with thrombolysis in a subregional setting covering full calendar years with a clear study catchment drawn serving as a confirmatory statistical analysis from the northeast of England in the last 2 years. Data between 16 June, 2013 and 15 June, 2015 were extracted from Sentinel Stroke National Audit Programme in Northumbria Healthcare NHS Foundation Trust that has covered health service for Northumberland and North Tyneside. The very old people aged 80 and above were less likely to have thrombolysis treatment, while there was no sex difference observed. Moreover, thrombolysis treatment was more likely to be given in ischemic patients with severe stroke symptoms. There was no difference in comorbidities including atrial fibrillation, congestive heart failure, diabetes, hypertension, and stroke/TIA as well. Those who received thrombolysis treatment were more likely to have atrial fibrillation or die at discharge. The ORs were higher after additionally adjusting for comorbidities. Similarly, these patients also had poorer scoring in modified Rankin scale than those who did not receive thrombolysis treatment. However, there was no difference at 6 months after survival. For future research, clinical outcomes in addition to atrial fibrillation and quality of life both at discharge and 6 months after thrombolysis treatment should be included for examination as well. For clinical practice, giving thrombolysis treatment in hospitals might need to be reconsidered if clinical outcomes were actually worse than not. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Thrombolysis in Postoperative Stroke.

PubMed

Voelkel, Nicolas; Hubert, Nikolai Dominik; Backhaus, Roland; Haberl, Roman Ludwig; Hubert, Gordian Jan

2017-11-01

Intravenous thrombolysis (IVT) is beneficial in reducing disability in selected patients with acute ischemic stroke. There are numerous contraindications to IVT. One is recent surgery. The aim of this study was to analyze the safety of IVT in patients with postoperative stroke. Data of consecutive IVT patients from the Telemedical Project for Integrative Stroke Care thrombolysis registry (February 2003 to October 2014; n=4848) were retrospectively searched for keywords indicating preceding surgery. Patients were included if surgery was performed within the last 90 days before stroke. The primary outcome was defined as surgical site hemorrhage. Subgroups with major/minor surgery and recent/nonrecent surgery (within 10 days before IVT) were analyzed separately. One hundred thirty-four patients underwent surgical intervention before IVT. Surgery had been performed recently (days 1-10) in 49 (37%) and nonrecently (days 11-90) in 85 patients (63%). In 86 patients (64%), surgery was classified as major, and in 48 (36%) as minor. Nine patients (7%) developed surgical site hemorrhage after IVT, of whom 4 (3%) were serious, but none was fatal. One fatal bleeding occurred remotely from surgical area. Rate of surgical site hemorrhage was significantly higher in recent than in nonrecent surgery (14.3% versus 2.4%, respectively, odds ratio adjusted 10.73; 95% confidence interval, 1.88-61.27). Difference between patients with major and minor surgeries was less distinct (8.1% and 4.2%, respectively; odds ratio adjusted 4.03; 95% confidence interval, 0.65-25.04). Overall in-hospital mortality was 8.2%. Intracranial hemorrhage occurred in 9.7% and was asymptomatic in all cases. IVT may be administered safely in postoperative patients as off-label use after appropriate risk-benefit assessment. However, bleeding risk in surgical area should be taken into account particularly in patients who have undergone surgery shortly before stroke onset. © 2017 American Heart Association, Inc.

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.

Thrombolysis and neuroprotection in cerebral ischemia.

PubMed

Gutiérrez, M; Díez Tejedor, E; Alonso de Leciñana, M; Fuentes, B; Carceller, F; Roda, J M

2006-01-01

Stroke is a major cause of death and disability worldwide. The resulting burden on society grows with the increase in the incidence of stroke. The term brain attack was introduced to describe the acute presentation of stroke and emphasize the need for urgent action to remedy the situation. Though a large number of therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or are being evaluated, there is still a large gap between the benefits of these agents and the properties of an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour time window has been shown to improve the outcome of patients with ischemic stroke. Understanding the mechanisms of injury and neuroprotection in these diseases is important to target news sites for treating ischemia. Better evaluation of the drugs and increased similarity between the results of animal experimentation and in the clinical setting requires critical assessment of the selection of animal models and the parameters to be evaluated. Our laboratory has employed a rat embolic stroke model to investigate the combination of rtPA with citicoline as compared to monotherapy alone and investigated whether neuroprotection should be provided before or after thrombolysis in order to achieve a greater reduction of ischemic brain damage. Copyright 2006 S. Karger AG, Basel.

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

High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke.

PubMed

Burgess, Alison; Huang, Yuexi; Waspe, Adam C; Ganguly, Milan; Goertz, David E; Hynynen, Kullervo

2012-01-01

It is estimated that only 2-6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed that the sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments.

High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke

PubMed Central

Burgess, Alison; Huang, Yuexi; Waspe, Adam C.; Ganguly, Milan; Goertz, David E.; Hynynen, Kullervo

2012-01-01

It is estimated that only 2–6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed thatthe sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments. PMID:22870315

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.

[Intravenous thrombolysis for acute ischemic stroke. A four years’ experience in a Chilean public hospital].

PubMed

Soto V, Álvaro; Morales I, Gladys; Grandjean B, Marcela; Pollak W, Débora; Del Castillo C, Carolina; García F, Pía; Von Johnn A, Alexis; Riquelme G, Alfonso

2017-04-01

Intravenous thrombolysis (IVT) with alteplase (tissue plasminogen activator) is the standard pharmacological treatment in acute ischemic stroke (AIS), reducing disability in patients. To report the results a thrombolysis protocol during four years in a regional public hospital. Data from 106 consecutive patients aged 68 ± 13 years (57% men) who were treated with IVT, from May 2012 until April 2016, was analyzed. The median door-to-needle time was 80 minutes (interquartile range = 57-113). The median National Institute of Health Stroke Scale (NIHSS) scores on admission and at discharge were was 11.5 and 5 points respectively. At discharge, 27% of hospitalized patients had a favorable outcome (n = 99), defined as having 0 to 1 points in the modified Rankin scale. Symptomatic intracerebral hemorrhage and mortality rates were 5.7 and 13.1%, respectively. The thrombolysis rate rose from 0.7% in 2012 to 6% in 2016. The implementation of 24/7 neurology shifts in the Emergency Department allowed us to increase the amount and quality of IVT in our hospital, as measured by the rate of thrombolysis and by process indicators such as door-to-needle time.

Thrombolysis and outcome of young stroke patients over the last decade: insights from the Nationwide Inpatient Sample.

PubMed

Kansara, Amit; Chaturvedi, Seemant; Bhattacharya, Pratik

2013-08-01

A recent study found a trend toward increasing hospitalizations for acute ischemic stroke (AIS) among young adults, raising concern for this subgroup. In the present study, we evaluated trends of use of thrombolysis and outcome among young adults (19-44 years of age) with AIS using a nationally representative administrative database. Discharge data were obtained from Nationwide Inpatient Sample between 2001 and 2009. Hospitalizations with a discharge diagnosis of AIS for patients 19 to 44 years of age were included. Use of thrombolysis was determined within this subset. The Cochran-Armitage test was used for trend analysis. Thrombolysis in young patients with AIS increased from 354 (1.84%) in 2001 to 1,237 (4.97%) in 2009 (P < .0001). The highest increase was noted at urban teaching hospitals. There was a progressive decrease in mortality in young AIS patients, from 6.81% in 2001 to 5.43% in 2009 (trend P = .027) and significant increase in discharges to rehabilitation (3.42% in 2002 to 12.7% in 2009 [trend P < .0001]). Discharge to other facilities decreased significantly (29.1% in 2001 to 17.8% in 2009 [trend P < .0001]). The rate of intracranial hemorrhage (2.70% in 2001; 2.69% in 2009) did not show any significant change despite the increase in the use of thrombolysis (trend P = .39). The rate of thrombolysis among young patients with AIS increased significantly between 2001 and 2009. A decrease in deaths with increased rehabilitation placements of young patients with AIS was noted over the last decade, suggesting improving outcomes. The lower rate of use of thrombolysis in rural hospitals may be improved with the widespread use of telestroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.

PubMed

Cappellari, Manuel; Moretto, Giuseppe; Micheletti, Nicola; Donato, Francesco; Tomelleri, Giampaolo; Gulli, Giosuè; Carletti, Monica; Squintani, Giovanna Maddalena; Zanoni, Tiziano; Ottaviani, Sarah; Romito, Silvia; Tommasi, Giorgio; Musso, Anna Maria; Deotto, Luciano; Gambina, Giuseppe; Zimatore, Domenico Sergio; Bovi, Paolo

2014-05-01

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different

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

Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

PubMed

Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

2017-04-03

Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. 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.

Functional outcome after primary endovascular therapy or IV thrombolysis alone for stroke. An observational, comparative effectiveness study.

PubMed

Abilleira, Sònia; Ribera, Aida; Dávalos, Antonio; Ribó, Marc; Chamorro, Angel; Cardona, Pere; Molina, Carlos A; Martínez-Yélamos, Antonio; Urra, Xabier; Dorado, Laura; Roquer, Jaume; Martí-Fàbregas, Joan; Aja, Lucía; Tomasello, Alejandro; Castaño, Carlos; Blasco, Jordi; Cánovas, David; Castellanos, Mar; Krupinski, Jerzy; Guimaraens, Leopoldo; Perendreu, Joan; Ustrell, Xavier; Purroy, Francisco; Gómez-Choco, Manuel; Baiges, Joan Josep; Cocho, Dolores; Saura, Júlia; Gallofré, Miquel

2014-01-01

Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score

Effects of golden hour thrombolysis: a Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy.

PubMed

Ebinger, Martin; Kunz, Alexander; Wendt, Matthias; Rozanski, Michal; Winter, Benjamin; Waldschmidt, Carolin; Weber, Joachim; Villringer, Kersten; Fiebach, Jochen B; Audebert, Heinrich J

2015-01-01

The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the golden hour. To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome. The prospective controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin, Germany, within an established infrastructure for stroke care. Weeks were randomized according to the availability of a specialized ambulance (stroke emergency mobile unit (STEMO) from May 1, 2011, through January 31, 2013. We included 6182 consecutive adult patients for whom a stroke dispatch (44.1% male; mean [SD] age, 73.9 [15.0] years) or regular care (45.0% male; mean [SD] age, 74.2 [14.9] years) were included. The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls. If STEMO was not available (during control weeks, when the unit was already in operation, or during maintenance), patients received conventional care. The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection. The unit is staffed with a neurologist trained in emergency medicine, a paramedic, and a technician. Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found. Rates of golden hour thrombolysis, 7- and 90-day mortality, secondary intracerebral hemorrhage, and discharge home. Thrombolysis rates in ischemic stroke were 200 of 614 patients (32.6%) when STEMO was deployed and 330 of 1497 patients (22.0%) when conventional care was administered (P < .001). Among all patients who received thrombolysis, the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment (62 of 200 patients [31.0%] vs 16 of 330 [4.9%]; P < .01). Compared with patients with a longer time from symptom onset to

Catheter-Directed Thrombolysis of Acute Deep Vein Thrombosis in the Lower Extremity of a Child with Interrupted Inferior Vena Cava

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

Oguzkurt, Levent, E-mail: loguzkurt@yahoo.com; Ozkan, Ugur; Tercan, Fahri

2007-04-15

We present the case of a 14-year-old girl who developed acute deep vein thrombosis (DVT) in her right lower extremity. Laboratory testing revealed protein S deficiency, and the patient's father also had this abnormality with a history of lower extremity DVT. Manual thromboaspiration followed by catheter-directed thrombolysis resulted in total clearance of all thrombi. Computed tomography and later venography revealed an interrupted inferior vena cava. Catheter-directed thrombolysis is an established treatment for adults with acute DVT. To the best of our knowledge, this report is the first to describe catheter-directed thrombolysis in a pediatric patient with lower extremity DVT. Ourmore » results suggest that catheter-directed thrombolysis is safe and effective for use in selected older children and adolescents with acute DVT in the lower extremity.« less

Diagnosis and treatment of shock due to massive pulmonary embolism: approach with transesophageal echocardiography and intrapulmonary thrombolysis.

PubMed

Krivec, B; Voga, G; Zuran, I; Skale, R; Pareznik, R; Podbregar, M; Noc, M

1997-11-05

To evaluate the diagnostic value of transesophageal echocardiography (TEE) as an initial diagnostic tool in shocked patients. The second objective was to study therapeutic impact of intrapulmonary thrombolysis in patients with diagnosed massive pulmonary embolism. Prospective observational study. Medical ICU in 800-bed general hospital. Twenty-four consecutive patients with unexplained shock and distended jugular veins. In 18 patients, right ventricular dilatation with global or segmental hypokinesis was documented. In addition, central pulmonary thromboemboli (12 patients), reduced contrast flow in right pulmonary artery (one patient), and right ventricular free wall akinesis (one patient) were found. No additional echocardiographic findings were apparent in four patients. According to pulmonary scintigraphy or autopsy, sensitivity of TEE for diagnosis of massive pulmonary embolism (MPE) in patients with right ventricular dilatation was 92% and specificity was 100%. In patients without right ventricular dilatation, left ventricular dysfunction (four patients) or cardiac tamponade (two patients) was confirmed. Intrapulmonary thrombolysis was evaluated in 11 of 13 patients with MPE. Two patients died prior to attempted thrombolysis. Three patients received streptokinase and eight received urokinase. Twenty-four hours after beginning of treatment, total pulmonary resistance index significantly decreased for 59% and mean pulmonary artery pressure for 31%. Cardiac index increased for 74%. Nine of 11 patients receiving thrombolysis survived to hospital discharge. Bedside TEE is a valuable tool for diagnosis of MPE. It enables immediate intrapulmonary thrombolysis, which seems to be an effective therapeutic alternative in our group of patients with obstructive shock.

The free-radical scavenger edaravone accelerates thrombolysis with alteplase in an experimental thrombosis model.

PubMed

Yamashita, Tsutomu; Sato, Takumi; Sakamoto, Kumi; Ishii, Hiromitsu; Yamamoto, Junichiro

2015-06-01

Reperfusion injury after thrombolytic therapy can have adverse neurologic effects. The free-radical scavenger edaravone is used in combination with the recombinant tissue plasminogen activator alteplase to treat acute ischemic stroke. However, basic investigations of this combination use remain inadequate. Here, we used an in vivo model to investigate the effects of edaravone on alteplase-induced thrombolysis. Thrombolysis was evaluated by using a He-Ne-laser-induced thrombosis model in rat mesenteric microvessels. Changes in thrombus volume were analyzed with the image analysis software Image-Pro Plus (Media Cybernetics, USA). There were three experimental groups (placebo, alteplase 0.6 mg/kg, alteplase 0.6 mg/kg + edaravone 10.5 mg/kg). Sequential changes (0 to 60 min) in thrombus volume were compared by using a relative optical density method that we had used previously. In the placebo group, the thrombus volume at 60 min, reflecting the extent of thrombolysis, was 97.2% ± 5.7% of the initial value. In the alteplase group, thrombus volume decreased to 70.7% ± 4.1% (P<0.01) after 20 min and 14.2% ± 6.6% after 60 min. In the alteplase+edaravone group, thrombus volume decreased to 66.9% ± 7.2% (P<0.001) after 10 min and 10.9% ± 2.3% after 60 min. These results support the hypothesis that edaravone accelerates thrombolysis by alteplase. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Prehospital Thrombolysis in Stroke Patients With Prestroke Dependency.

PubMed

Nolte, Christian H; Ebinger, Martin; Scheitz, Jan F; Kunz, Alexander; Erdur, Hebun; Geisler, Frederik; Braemswig, Tim-Bastian; Rozanski, Michal; Weber, Joachim E; Wendt, Matthias; Zieschang, Katja; Fiebach, Jochen B; Villringer, Kersten; Grittner, Ulrike; Kaczmarek, Sabina; Endres, Matthias; Audebert, Heinrich J

2018-03-01

Data on effects of intravenous thrombolysis on outcome of patients with ischemic stroke who are dependent on assistance in activities of daily living prestroke are scarce. Recent registry based analyses in activities of daily -independent patients suggest that earlier start of intravenous thrombolysis in the prehospital setting leads to better outcomes when compared with the treatment start in hospital. We evaluated whether these observations can be corroborated in patients with prestroke dependency. This observational, retrospective analysis included all patients with acute ischemic stroke depending on assistance before stroke who received intravenous thrombolysis either on the Stroke Emergency Mobile (STEMO) or through conventional in-hospital care (CC) in a tertiary stroke center (Charité, Campus Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable logistic regression. Between February 2011 and March 2015, 122 of 427 patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC needed assistance before stroke. Median onset-to-treatment times were 97 (interquartile range, 69-159; STEMO) and 135 (interquartile range, 98-184; CC; P <0.001) minutes. After 3 months, modified Rankin Scale scores of 0 to 3 was observed in 48 STEMO patients (39%) versus 35 CC patients (25%; P =0.01) and 86 (70%, STEMO) versus 85 (60%, CC) patients were alive ( P =0.07). After adjustment, STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3 (odds ratio, 1.99; 95% confidence interval, 1.02-3.87; P =0.042) with a nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval, 0.95-3.16; P =0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO versus 12 CC patients (4.2% versus 8.5%; P =0.167). The results of this study suggest that earlier, prehospital

Do lacunar strokes benefit from thrombolysis? Evidence from the Registry of the Canadian Stroke Network.

PubMed

Shobha, Nandavar; Fang, Jiming; Hill, Michael D

2013-10-01

Lacunar infarcts constitute up to 25% of all ischaemic strokes. As acute intracranial vascular imaging has become widely available with computed tomographic angiography, thrombolysis of lacunar strokes has become contentious because an intracranial vascular lesion cannot be visualized. We studied the effect of thrombolysis on lacunar strokes compared to other clinical ischaemic stroke sub-types. Ischaemic stroke patients from phase 3 of the Registry of the Canadian Stroke Network data (July 2003-March 2008) were included. Lacunar stroke was defined as a lacunar syndrome supported by computed tomography brain showing a subcortical hypodense lesion with a diameter <20 mm. Clinical syndromes were used to define other stroke sub-types. The outcomes were mortality at 90 days, modified Rankin Scale score 0-2 at discharge, occurrence of intracranial haemorrhage as a complication of stroke in-hospital, and discharge disposition to home. A total of 11,503 patients of ischaemic stroke were included from the Registry of the Canadian Stroke Network 3 between July 2003 and March 2008. Lacunar strokes formed 19.1% of the total strokes. The total number of patients who received tissue plasminogen activator was 1630 (14.2%). A significant association was found between tissue plasminogen activator treatment and outcomes after controlling Oxfordshire Community Stroke Project types--for modified Rankin Scale at discharge and discharge to home, but not for mortality. A thrombolysis-by-Oxfordshire Community Stroke Project stroke sub-type interaction was observed due to lack of benefit among the posterior circulation stroke sub-types. Patients with lacunar strokes, partial anterior circulation stroke, and total anterior circulation strokes all benefited approximately equally from thrombolysis. Thrombolysis is associated with clinically improved outcome among patients with lacunar stroke syndromes. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

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.

Generalized Safety and Efficacy of Simplified Intravenous Thrombolysis Treatment (SMART) Criteria in Acute Ischemic Stroke: The MULTI SMART Study.

PubMed

Sørensen, Sigrid B; Barazangi, Nobl; Chen, Charlene; Wong, Christine; Grosvenor, David; Rose, Jack; Bedenk, Ann; Morrow, Megan; McDermott, Dan; Hove, Jens D; Tong, David C

2016-05-01

Common intravenous recombinant tissue plasminogen activator (IV rt-PA) exclusion criteria may substantially limit the use of thrombolysis. Preliminary data have shown that the SMART (Simplified Management of Acute stroke using Revised Treatment) criteria greatly expand patient eligibility by reducing thrombolysis exclusions, but they have not been assessed on a large scale. We evaluated the safety and efficacy of general adoption of SMART thrombolysis criteria to a large regional stroke network. Retrospective analysis of consecutive patients who received IV thrombolysis within a regional stroke network was performed. Patients were divided into those receiving thrombolysis locally versus at an outside hospital. The primary outcome was modified Rankin Scale score (≤1) at discharge and the main safety outcome was symptomatic intracranial hemorrhage (sICH) rate. There were 539 consecutive patients, and 50.5% received thrombolysis at an outside facility. Ninety percent of the patients possessed common conventional IV rt-PA contraindications. There were no significant differences between local and network treated patients in favorable outcome (45.4% versus 37.4%; odds ratio [OR], .72; P > .09), mortality (9% versus 14%; OR, 1.6; P > .07), or sICH rate (2.6% versus 5.1%; OR, 2.0; P = .13). Multivariate analysis showed no association between receiving IV rt-PA at an outlying spoke hospital and higher rate of sICH or worse outcome at discharge. Generalized application of SMART criteria is safe and effective. Widespread application of these criteria could substantially increase the proportion of patients who might qualify for treatment. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

PubMed

Sun, Li; Zhou, Wei; Mueller, Christian; Sommer, Clemens; Heiland, Sabine; Bauer, Alexander T; Marti, Hugo H; Veltkamp, Roland

2010-09-01

Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n=96) breathed either air, 100% O(2) (NBO), or 100% O(2) at 3 bar (HBO) for 1 hour. Immediately thereafter, recombinant tissue plasminogen activator (rt-PA, 9 mg/kg) was injected. Although significant reperfusion was observed after thrombolysis in TT-tMCAO, vascular occlusion persisted in CT-tMCAO. In TT-tMCAO, NBO and HBO significantly reduced diffusion-weighted imaging-magnetic resonance imaging (MRI) lesion volume and postischemic blood-brain barrier (BBB) permeability on postcontrast T1-weighted images. NBO and, significantly more potently, HBO reduced macroscopic hemorrhage on T2* MRI and on corresponding postmortem cryosections. Oxygen therapy lowered hemoglobin content and attenuated activation of matrix metalloproteinases in the ischemic hemisphere. In contrast, NBO and HBO failed to reduce infarct size in CT but both decreased BBB damage and microscopic hemorrhagic transformation. Only HBO reduced hemoglobin extravasation in the ischemic hemisphere. In conclusion, NBO and HBO decrease infarct size after thromboembolic ischemia only if recanalization is successful. As NBO and HBO also reduce postthrombolytic intracerebral hemorrhage, combining the two with thrombolysis seems promising.

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.

Changing paradigms in thrombolysis in acute myocardial infarction.

PubMed

Gotsman, M S; Rozenman, Y; Admon, D; Mosseri, M; Lotan, C; Zahger, D; Weiss, A T

1997-05-23

Acute myocardial infarction occurs when a ruptured coronary artery plaque causes sudden thrombotic occlusion of a coronary artery and cessation of coronary artery blood flow. This paper reviews the underlying coronary pathology in progressive coronary atherosclerosis, mechanisms of plaque rupture and arterial occlusion and the time relationship between coronary occlusion and myocardial necrosis. Reperfusion can be achieved by chemical thrombolysis with different thrombolytic agents. Early lysis is achieved best by prehospital administration, a transtelephonic monitor, a mobile intensive care unit, active general practitioner treatment or by warning the emergency room of impending arrival of a patient. Thrombolytic therapy may be unsuccessful and not achieve Grade III TIMI flow in less than 4 h (or even 2 h) due to inadequate or intermittent perfusion or reocclusion. Adjuvant therapy includes aspirin and platelet receptor antagonists. Bleeding is a constant danger. Direct percutaneous transluminal coronary angioplasty (PTCA) may be as effective or better than chemical thrombolysis. Reperfusion protects the myocardium and salvages viable tissue. It also improves mechanical remodelling of the ventricle. Long-term follow-up has shown that quantum leaps of fresh coronary occlusion causes step-wise progression in patient disability and that further early, prompt reperfusion can salvage myocardium and prevent this inexorable progress of the disease.

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.

Combined Pharmacomechanical Thrombolysis of Complete Portomesenteric Thrombosis in a Liver Transplant Recipient

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

Lorenz, Jonathan M., E-mail: jlorenz@radiology.bsd.uchicago.edu; Bennett, Shelby; Patel, Jay

2013-01-30

Treatment options for portomesenteric venous thrombosis range from anticoagulation to surgery, depending on chronicity, severity of symptoms, extent of thrombosis, and the availability of local expertise. For acute and subacute cases, a variety of endovascular options have been described in limited published series and case reports, including thrombolysis and mechanical thrombectomy. We report what is to our knowledge the first case in which the Trellis pharmacomechanical thrombolysis device was used successfully to treat complete acute thrombosis of the entire superior mesenteric vein and the entire portal vein with extension into all segmental intrahepatic portal branches in a young adult aftermore » liver transplantation. This device, coupled with adjunctive techniques using balloon catheters, facilitated complete restoration of flow, resulting in graft salvage and long-term patency.« less

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

Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study.

PubMed

Willeit, Johann; Geley, Theresa; Schöch, Johannes; Rinner, Heinrich; Tür, Andreas; Kreuzer, Hans; Thiemann, Norbert; Knoflach, Michael; Toell, Thomas; Pechlaner, Raimund; Willeit, Karin; Klingler, Natalie; Praxmarer, Silvia; Baubin, Michael; Beck, Gertrud; Berek, Klaus; Dengg, Christian; Engelhardt, Klaus; Erlacher, Thomas; Fluckinger, Thomas; Grander, Wilhelm; Grossmann, Josef; Kathrein, Hermann; Kaiser, Norbert; Matosevic, Benjamin; Matzak, Heinrich; Mayr, Markus; Perfler, Robert; Poewe, Werner; Rauter, Alexandra; Schoenherr, Gudrun; Schoenherr, Hans-Robert; Schinnerl, Adolf; Spiss, Heinrich; Thurner, Theresa; Vergeiner, Gernot; Werner, Philipp; Wöll, Ewald; Willeit, Peter; Kiechl, Stefan

2015-01-01

Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). During the period of

[Prehospital thrombolysis: A national perspective. Pharmaco-invasive strategy for early reperfusion of STEMI in Mexico].

PubMed

Arriaga-Nava, Roberto; Valencia-Sánchez, Jesús-Salvador; Rosas-Peralta, Martin; Garrido-Garduño, Martin; Calderón-Abbo, Moisés

2015-01-01

To review the existing evidence on the role of prehospital thrombolysis in patients with ST-segment elevation acute myocardial infarction (STEMI) as part of a strategy of cutting edge to reduce the time of coronary reperfusion and as a consequence improves both the survival and function. We used the technique of exploration-reduction-evaluation-analysis and synthesis of related studies, with an overview of current recommendations, data from controlled clinical trials and from the national and international registries about the different strategies for STEMI reperfusion. In total, we examined 186 references on prehospital thrombolysis, 130 references in times door-treatment, 139 references in STEMI management and national and international registries as well as 135 references on rescue and primary percutaneous coronary intervention for STEMI. Finally the 48 references that were more relevant and informative were retained. The «time» factor is crucial in the success of early reperfusion in STEMI especially if thrombolysis is applied correctly during the prehospital time. The primary percutaneous coronary intervention is contingent upon its feasibility before 120 min from the onset of symptoms. In our midst to internationally, thrombolysis continues to be a strategy with great impact on their expectations of life and function of patients. Telecommunication systems should be incorporate in real time to the priority needs of catastrophic diseases such as STEMI where life is depending on time. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

PubMed

Doheny, Charles; Gonzalez, Lorena; Duchman, Stanley M; Varon, Joseph; Bechara, Carlos F; Cheung, Mathew; Lin, Peter H

2018-06-01

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0

National use of thrombolysis with alteplase for acute ischaemic stroke via telemedicine in Denmark: a model of budgetary impact and cost effectiveness.

PubMed

Ehlers, Lars; Müskens, Wilhelmina Maria; Jensen, Lotte Groth; Kjølby, Mette; Andersen, Grethe

2008-01-01

The purpose of this analysis was to assess the budgetary impact and cost effectiveness of the national use of thrombolysis with alteplase (recombinant tissue plasminogen activator; rt-PA) for acute ischaemic stroke via telemedicine in Denmark. Computations were based on a Danish health economic model of thrombolysis treatment of acute ischaemic stroke via telemedicine. Cost data for stroke units and satellite clinics were taken from the first practical experiences in Denmark with implementing thrombolysis via telemedical linkage to the Stroke Department at Aarhus University Hospital. Effectiveness data were taken from a published pooled analysis of results from randomized controlled trials of alteplase. The calculations showed that the additional total costs to the hospitals of implementing thrombolysis with alteplase for acute ischaemic stroke via telemedicine were approximately $US3.0 (range 2.0-5.8) million per year in the case of five centres and five satellite clinics, or $US3.6 (range 2.4-7.0) million per year based on seven centres and seven satellite clinics. The incremental cost-effectiveness ratio was calculated to be approximately $US50,000 when taking a short time perspective (1 year), but thrombolysis was dominant (both cheaper and more effective) after as little as 2 years and cost effectiveness improved over longer time scales. The budgetary impact of using thrombolysis with alteplase for acute ischaemic stroke via telemedicine depends on the existing capacity and organizational conditions at the local hospitals. The health economic model computations suggest that the macroeconomic costs may balance with savings in care and rehabilitation after as little as 2 years, and that potentially large long-term savings are associated with thrombolysis with alteplase delivered by telemedicine, although the long-term calculations are uncertain.

Intra-arterial thrombolysis of digital artery occlusions in a patient with polycythemia vera.

PubMed

Jud, Philipp; Hafner, Franz; Gary, Thomas; Ghanim, Leyla; Lipp, Rainer; Brodmann, Marianne

2017-01-01

There are limited therapeutic options for the resolution of digital artery occlusions. Intra-arterial thrombolysis with anticoagulative and thrombolytic drugs successfully restored the blood flow in the affected digital arteries.

Synthetic thrombus model for in vitro studies of laser thrombolysis

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

Hermes, R.E.; Trajkovska, K.

1998-07-01

Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. The authors describe the development of new surrogate materials based on formulations incorporating chick egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and humanmore » (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.« less

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.

Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review.

PubMed

Desilles, Jean-Philippe; Meseguer, Elena; Labreuche, Julien; Lapergue, Bertrand; Sirimarco, Gaia; Gonzalez-Valcarcel, Jaime; Lavallée, Philippa; Cabrejo, Lucie; Guidoux, Celine; Klein, Isabelle; Amarenco, Pierre; Mazighi, Mikael

2013-07-01

The potential detrimental effect of diabetes mellitus and admission glucose level (AGL) on outcomes after stroke thrombolysis is unclear. We evaluated outcomes of patients treated by intravenous and/or intra-arterial therapy, according to diabetes mellitus and AGL. We analyzed data from a patient registry (n=704) and conducted a systematic review of previous observational studies. The primary study outcome was the percentage of patients who achieved a favorable outcome (modified Rankin score ≤2 at 3 months). We identified 54 previous reports that evaluated the effect of diabetes mellitus or AGL on outcomes after thrombolysis. In an unadjusted meta-analysis that included our registry data and previous available observational data, diabetes mellitus was associated with less favorable outcome (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.73-0.79) and more symptomatic intracranial hemorrhage (OR, 1.38; 95% CI, 1.21-1.56). However, in multivariable analysis, diabetes mellitus remained associated with less favorable outcome (OR, 0.77; 95% CI, 0.69-0.87) but not with symptomatic intracranial hemorrhage (OR, 1.11; 95% CI, 0.83-1.48). In unadjusted and in adjusted meta-analysis, higher AGL was associated with less favorable outcome and more symptomatic intracranial hemorrhage; the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.92 (0.90-0.94) for favorable outcome, and 1.09 (1.04-1.14) for symptomatic intracranial hemorrhage. These results confirm that AGL and history of diabetes mellitus are associated with poor clinical outcome after thrombolysis. AGL may be a surrogate marker of brain infarction severity rather than a causal factor. However, randomized controlled evidences are needed to address the significance of a tight glucose control during thrombolysis on clinical outcome.

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.

Intravenous thrombolysis with recombinant tissue plasminogen activator in vascular warning syndromes.

PubMed

González Hernández, A; Fabre Pi, O; Cabrera Naranjo, F; López Veloso, A C

2014-01-01

Vascular warning syndromes constitute a neurological emergency due to their associated high risk of established stroke. At present, there is no strong evidence indicating the best treatment for these patients. The aim of this paper is to describe the function of intravenous rt-PA thrombolysis in the treatment of vascular warning syndromes. We reviewed our hospital records and the literature to find patients with neurologically fluctuating profiles and who underwent intravenous rt-PA thrombolysis. We retrieved 3 cases from our hospital records and 19 from the literature (15 males and 7 females). Mean age was 68.7±9 years (range: 52-84 years). The mean number of episodes before treatment was 4 (range: 2-15 episodes). The maximum NIHSS scores ranged from 6 to 22 in different patients. We obtained 24-hour post-treatment NIHSS scores in 8 cases; of these cases, 6 (75%) had a score of 0, and the other 2 (25%) had a score of 12. The Modified Rankin Score calculated at 3 months of treatment was 0 or 1 in 18 patients (81.8%); these 18 comprised 8 of the 10 patients with lacunar warning syndromes (80%), 6 of the 7 with basilar warning syndromes (85.7%), and 4 of the 5 with fluctuating non-lacunar, non-basilar warning syndromes (80%). Intravenous rt-PA treatment may constitute an effective and safe therapeutic alternative for patients with neurovascular fluctuations. However, well-designed studies are needed to determine the role of intravenous rt-PA thrombolysis in cases of vascular warning syndrome. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Thrombolysis in the age of Primary Percutaneous Coronary Intervention: Mini-Review and Meta-analysis of Early PCI.

PubMed

Al Shammeri, O; Garcia, LA

2013-01-01

Primary Percutaneous Coronary Intervention (PCI) is the treatment of choice for ST-segment Elevation Myocardial Infarction (STEMI) if performed within 90 minutes from first medical contact. However, primary PCI is only available for less than 25% of patients with STEMI. Early PCI or Pharmaco-invasive strategy has evolved from facilitated PCI but with more delayed timing from thrombolysis to PCI. Assess the safety and effectiveness of Early PCI. We reviewed the data of the available therapy options for patients with STEMI. Then we performed a meta-analysis for all randomized controlled trials of early PCI versus standard therapy. Five studies fulfilled our inclusion criteria. Our meta-analysis showed improved cardiovascular events with early PCI compared to standard therapy (odd ratio of 0.54; 95% Confidence interval 0.47-0.7, p<0.001). There were no significant bleeding complications when doing early PCI 4 to 24 hours after successful thrombolysis. Early PCI should be done to all STEMI patients within 24 hours after successful thrombolysis.

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

Minimum intravenous thrombolysis utilization rates in acute ischemic stroke to achieve population effects on disability: A discrete-event simulation model.

PubMed

Hoffmeister, Lorena; Lavados, Pablo M; Mar, Javier; Comas, Merce; Arrospide, Arantzazu; Castells, Xavier

2016-06-15

The only pharmacological treatment with proven cost-effectiveness in reducing acute ischemic stroke (AIS) associated disability is intravenous thrombolysis with recombinant tissue plasminogen activator but it's utilization rate is still low in most of the world. We estimated the minimum thrombolysis utilization rate needed to decrease the prevalence of stroke-related disability at a population level by using a discrete-event simulation model. The model included efficacy according to time to treatment up to 4.5h, and four scenarios for the utilization of intravenous thrombolysis in eligible patients with AIS: a) 2%; b) 12% c) 25% and d) 40%. We calculated the prevalence of AIS related disability in each scenario, using population based data. The simulation was performed from 2002 to 2017 using the ARENA software. A 2% utilization rate yielded a prevalence of disability of 359.1 per 100,000. Increasing thrombolysis to 12% avoided 779 disabled patients. If the utilization rate was increased to 25%, 1783 disabled patients would be avoided. The maximum scenario of 40% decreased disability to 335.7 per 100,000, avoiding 17% of AIS-related disability. The current utilization rate of intravenous thrombolysis of 2% has minimal population impact. Increasing the rate of utilization to more than 12% is the minimum to have a significant population effect on disability and should be a public policy aim. Copyright © 2016 Elsevier B.V. All rights reserved.

Thrombolysis in the air. Air-ambulance paramedics flying to remote communities treat patients before hospitalization.

PubMed Central

Kapasi, H.; Kelly, L.; Morgan, J.

2000-01-01

PROBLEM ADDRESSED: First Nations* communities in the North have a high prevalence of coronary artery disease and type 2 diabetes and face an increasing incidence of myocardial infarction (MI). Many conditions delay timely administration of thrombolysis, including long times between when patients first experience symptoms and when they present to community nursing stations, delays in air transfers to treating hospitals, uncertainty about when planes are available, and poor flying conditions. OBJECTIVE OF PROGRAM: To develop a program for administration of thrombolysis on the way to hospital by air ambulance paramedics flying to remote communities to provide more rapid thrombolytic therapy to northern patients experiencing acute MIs. COMPONENTS OF PROGRAM: Critical care flight paramedics fly to northern communities from Sioux Lookout, Ont; assess patients; communicate with base hospital physicians; review an exclusion criteria checklist; and administer thrombolytics according to the Sioux Lookout District Health Centre/Base Hospital Policy and Procedure Manual. Patients are then flown to hospitals in Sioux Lookout; Winnipeg, Man; or Thunder Bay, Ont. CONCLUSION: This thrombolysis program is being pilot tested, and further evaluation and development is anticipated. Images p1316-a p1317-a p1317-b PMID:10907571

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.

National Practice Patterns of Obtaining Informed Consent for Stroke Thrombolysis.

PubMed

Mendelson, Scott J; Courtney, D Mark; Gordon, Elisa J; Thomas, Leena F; Holl, Jane L; Prabhakaran, Shyam

2018-03-01

No standard approach to obtaining informed consent for stroke thrombolysis with tPA (tissue-type plasminogen activator) currently exists. We aimed to assess current nationwide practice patterns of obtaining informed consent for tPA. An online survey was developed and distributed by e-mail to clinicians involved in acute stroke care. Multivariable logistic regression analyses were performed to determine independent factors contributing to always obtaining informed consent for tPA. Among 268 respondents, 36.7% reported always obtaining informed consent and 51.8% reported the informed consent process caused treatment delays. Being an emergency medicine physician (odds ratio, 5.8; 95% confidence interval, 2.9-11.5) and practicing at a nonacademic medical center (odds ratio, 2.1; 95% confidence interval, 1.0-4.3) were independently associated with always requiring informed consent. The most commonly cited cause of delay was waiting for a patient's family to reach consensus about treatment. Most clinicians always or often require informed consent for stroke thrombolysis. Future research should focus on standardizing content and delivery of tPA information to reduce delays. © 2018 American Heart Association, Inc.

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.

Intravenous thrombolysis and endovascular therapy for acute ischemic stroke with internal carotid artery occlusion: a systematic review of clinical outcomes.

PubMed

Mokin, Maxim; Kass-Hout, Tareq; Kass-Hout, Omar; Dumont, Travis M; Kan, Peter; Snyder, Kenneth V; Hopkins, L Nelson; Siddiqui, Adnan H; Levy, Elad I

2012-09-01

Strokes secondary to acute internal carotid artery (ICA) occlusion are associated with extremely poor prognosis. The best treatment approach to acute stroke in this setting is unknown. We sought to determine clinical outcomes in patients with acute ischemic stroke attributable to ICA occlusion treated with intravenous (IV) systemic thrombolysis or intra-arterial endovascular therapy. Using the PubMed database, we searched for studies that included patients with acute ischemic stroke attributable to ICA occlusion who received treatment with IV thrombolysis or intra-arterial endovascular interventions. Studies providing data on functional outcomes beyond 30 days and mortality and symptomatic intracerebral hemorrhage (sICH) rates were included in our analysis. We compared the proportions of patients with favorable functional outcomes, sICH, and mortality rates in the 2 treatment groups by calculating χ(2) and confidence intervals for odds ratios. We identified 28 studies with 385 patients in the IV thrombolysis group and 584 in the endovascular group. Rates of favorable outcomes and sICH were significantly higher in the endovascular group than the IV thrombolysis-only group (33.6% vs 24.9%, P=0.004 and 11.1% vs 4.9%, P=0.001, respectively). No significant difference in mortality rate was found between the groups (27.3% in the IV thrombolysis group vs 32.0% in the endovascular group; P=0.12). According to our systematic review, endovascular treatment of acute ICA occlusion results in improved clinical outcomes. A higher rate of sICH after endovascular treatment does not result in increased overall mortality rate.

Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients.

PubMed

Green, Alexander R; Carney, Dana R; Pallin, Daniel J; Ngo, Long H; Raymond, Kristal L; Iezzoni, Lisa I; Banaji, Mahzarin R

2007-09-01

Studies documenting racial/ethnic disparities in health care frequently implicate physicians' unconscious biases. No study to date has measured physicians' unconscious racial bias to test whether this predicts physicians' clinical decisions. To test whether physicians show implicit race bias and whether the magnitude of such bias predicts thrombolysis recommendations for black and white patients with acute coronary syndromes. An internet-based tool comprising a clinical vignette of a patient presenting to the emergency department with an acute coronary syndrome, followed by a questionnaire and three Implicit Association Tests (IATs). Study invitations were e-mailed to all internal medicine and emergency medicine residents at four academic medical centers in Atlanta and Boston; 287 completed the study, met inclusion criteria, and were randomized to either a black or white vignette patient. IAT scores (normal continuous variable) measuring physicians' implicit race preference and perceptions of cooperativeness. Physicians' attribution of symptoms to coronary artery disease for vignette patients with randomly assigned race, and their decisions about thrombolysis. Assessment of physicians' explicit racial biases by questionnaire. Physicians reported no explicit preference for white versus black patients or differences in perceived cooperativeness. In contrast, IATs revealed implicit preference favoring white Americans (mean IAT score = 0.36, P < .001, one-sample t test) and implicit stereotypes of black Americans as less cooperative with medical procedures (mean IAT score 0.22, P < .001), and less cooperative generally (mean IAT score 0.30, P < .001). As physicians' prowhite implicit bias increased, so did their likelihood of treating white patients and not treating black patients with thrombolysis (P = .009). This study represents the first evidence of unconscious (implicit) race bias among physicians, its dissociation from conscious (explicit) bias, and its

Insulin resistance is associated with a poor response to intravenous thrombolysis in acute ischemic stroke.

PubMed

Calleja, Ana I; García-Bermejo, Pablo; Cortijo, Elisa; Bustamante, Rosa; Rojo Martínez, Esther; González Sarmiento, Enrique; Fernández-Herranz, Rosa; Arenillas, Juan F

2011-11-01

Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis. We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥ 3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points. A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67-43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23-54.44]; P = 0.029). High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.

Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke

PubMed Central

Calleja, Ana I.; García-Bermejo, Pablo; Cortijo, Elisa; Bustamante, Rosa; Rojo Martínez, Esther; González Sarmiento, Enrique; Fernández-Herranz, Rosa; Arenillas, Juan F.

2011-01-01

OBJECTIVE Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis. RESEARCH DESIGN AND METHODS We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points. RESULTS A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67–43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23–54.44]; P = 0.029). CONCLUSIONS High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis. PMID:21911778

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.

Thrombolysis in the age of Primary Percutaneous Coronary Intervention: Mini-Review and Meta-analysis of Early PCI

PubMed Central

Al Shammeri, O; Garcia, LA

2013-01-01

Objective Primary Percutaneous Coronary Intervention (PCI) is the treatment of choice for ST-segment Elevation Myocardial Infarction (STEMI) if performed within 90 minutes from first medical contact. However, primary PCI is only available for less than 25% of patients with STEMI. Early PCI or Pharmaco-invasive strategy has evolved from facilitated PCI but with more delayed timing from thrombolysis to PCI. Aim Assess the safety and effectiveness of Early PCI. Patients and Method We reviewed the data of the available therapy options for patients with STEMI. Then we performed a meta-analysis for all randomized controlled trials of early PCI versus standard therapy Results Five studies fulfilled our inclusion criteria. Our meta-analysis showed improved cardiovascular events with early PCI compared to standard therapy (odd ratio of 0.54; 95% Confidence interval 0.47-0.7, p<0.001). There were no significant bleeding complications when doing early PCI 4 to 24 hours after successful thrombolysis Conclusion Early PCI should be done to all STEMI patients within 24 hours after successful thrombolysis. PMID:23559909

Perfusion computed tomography-guided intravenous thrombolysis for acute ischemic stroke beyond 4.5 hours: a case-control study.

PubMed

García-Bermejo, Pablo; Calleja, Ana I; Pérez-Fernández, Santiago; Cortijo, Elisa; del Monte, José M; García-Porrero, Miguel; Fe Muñoz, M; Fernández-Herranz, Rosario; Arenillas, Juan F

2012-01-01

Extending the therapeutic window of intravenous thrombolysis for acute ischemic stroke beyond the established 4.5-hour limit is of critical importance in order to increase the proportion of thrombolysed stroke patients. In this setting, the capacity of MRI to select acute stroke patients for reperfusion therapies in delayed time windows has been and is being tested in clinical trials. However, whether the more available and cost-effective perfusion computed tomography (PCT) may be useful to select candidates for delayed intravenous thrombolysis remains largely unexplored. We aimed to evaluate the safety and efficacy of PCT-guided intravenous thrombolysis beyond 4.5 h after stroke onset. We prospectively studied all consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA) in our stroke unit between January 2008 and December 2010. Patients treated within 0- 4.5 h were treated according to non-contrast CT (NCCT) criteria. Beyond 4.5 h, patients received intravenous tPA according to PCT criteria, i.e. an infarct core on cerebral blood volume (CBV) maps not exceeding one third of the middle cerebral artery (MCA) territory and tissue at risk as defined by mean transit time-CBV mismatch greater than 20%. Predetermined primary endpoints were symptomatic hemorrhagic transformation and favorable long-term outcome, while early neurological improvement and MCA recanalization were considered secondary endpoints. Statistical analysis included bivariate comparisons between the two groups for each endpoint and logistic regression models when significance was found in bivariate analyses. This study was approved by our local ethics committee. A total of 245 patients received intravenous thrombolysis. After the groups were matched by baseline National Institutes of Health Stroke Scale score, 172 patients treated at <4.5 h and 43 patients treated at >4.5 h were finally included. Early and late groups were comparable regarding baseline

The hydrodynamic and ultrasound-induced forces on microbubbles under high Reynolds number flow representative of the human systemic circulation

NASA Astrophysics Data System (ADS)

Clark, Alicia; Aliseda, Alberto

2016-11-01

Ultrasound contrast agents (UCAs) are micron-sized bubbles that are used in conjunction with ultrasound (US) in medical applications such as thrombolysis and targeted intravenous drug delivery. Previous work has shown that the Bjerknes force, due to the phase difference between the incoming US pressure wave and the bubble volume oscillations, can be used to manipulate the trajectories of microbubbles. Our work explores the behavior of microbubbles in medium sized blood vessels under both uniform and pulsatile flows at a range of physiologically relevant Reynolds and Womersley numbers. High speed images were taken of the microbubbles in an in-vitro flow loop that replicates physiological flow conditions. During the imaging, the microbubbles were insonified at different diagnostic ultrasound settings (varying center frequency, PRF, etc.). An in-house Lagrangian particle tracking code was then used to determine the trajectories of the microbubbles and, thus, a dynamic model for the microbubbles including the Bjerknes forces acting on them, as well as drag, lift, and added mass. Preliminary work has also explored the behavior of the microbubbles in a patient-specific model of a carotid artery bifurcation to demonstrate the feasibility of preferential steering of microbubbles towards the intracranial circulation with US.

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.

Spontaneous Splenic Rupture Following Intravenous Thrombolysis with Alteplase Applied as Stroke Therapy – Case Report and Review of Literature

PubMed Central

Aleksic-Shihabi, Anka; Jadrijevic, Eni; Milekic, Nina; Bulicic, Ana Repic; Titlic, Marina; Suljic, Enra

2016-01-01

Introduction: Stroke is a medical emergency in neurology, and is one of the leading causes of death nowadays. At a recent time, a therapeutic method used in adequate conditions is thrombolysis, a treatment of an emerging clot in the brain vascular system by alteplase. The application of alteplase also has a high risk of life threatening conditions. Case report: This is a brief report of a case with thrombolysis complication which manifested as a spleen rupture. PMID:26980937

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...

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial

PubMed Central

Koga, Masatoshi; Toyoda, Kazunori; Kimura, Kazumi; Yamamoto, Haruko; Sasaki, Makoto; Hamasaki, Toshimitsu; Kitazono, Takanari; Aoki, Junya; Seki, Kenta; Homma, Kazunari; Sato, Shoichiro; Minematsu, Kazuo

2014-01-01

Rationale Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset. Aims The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment. Design This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment. Study outcomes The primary efficacy end-point is modified Rankin Scale 0–1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22–36 h, and major bleeding and mortality at 90 days. Discussion This trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time. PMID:25088843

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.

A one-to-one telestroke network: the first Italian study of a web-based telemedicine system for thrombolysis delivery and patient monitoring.

PubMed

Nardetto, Lucia; Dario, Claudio; Tonello, Simone; Brunelli, Marta Carla; Lisiero, Manola; Carraro, Maria Grazia; Saccavini, Claudio; Scannapieco, Gianluigi; Giometto, Bruno

2016-05-01

Over 10 years after European approval, thrombolysis is still limited by a restricted time window and non-optimal territorial coverage. Implementation of telestroke can give a growing number of patients access to treatment. We hereby present the first Italian telemedicine study applied to both the acute and the monitoring phase of stroke care. From January 2011 to December 2013, we tested a web-based, drip, and treat interaction model, connecting the cerebrovascular specialist of one hub center to the Emergency Department of a Spoke center. We then compared thrombolysis delivered using the telestroke model with thrombolysis provided at the Hub Stroke Unit at the time when the telemedicine program was activated. Telethrombolysis data were then compared with data from the two main international telestroke projects (TEMPiS and REACH), and other European telestroke studies performed at the time of writing. We collected a total of 131 thrombolysis procedures (25 telethrombolysis and 106 thrombolysis patients at the Stroke Unit). Statistical analysis with the t test yielded no statistically significant differences between the two populations in door-to-scan, door-to-needle (DTN), and onset-to-treatment times (OTT). Our OTT and DTN pathway times were longer than the TEMPiS and REACH studies but comparable with other European telemedicine trials, despite different models of interaction and number of centers. Our study in a northeastern province of Italy confirms the potential of applying telemedicine to a cerebrovascular pathology.

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

Fibrin-Targeted Magnetic Resonance Imaging Allows In Vivo Quantification of Thrombus Fibrin Content and Identifies Thrombi Amenable for Thrombolysis

PubMed Central

Jenkins, Julia; Modarai, Bijan; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Grover, Steven P.; Patel, Ashish S.; Schaeffter, Tobias; Smith, Alberto; Botnar, Rene M.

2014-01-01

Objective Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus’ fibrin content in vivo and for the identification of thrombus suitable for thrombolysis. Approach and Results Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus’ histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R2=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre–EP-2104R and post–EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97–1.00] and 0.994 [95% confidence interval, 0.98–1.00] respectively). Conclusions MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. PMID:24723557

Budget impact analysis of thrombolysis for stroke in Spain: a discrete event simulation model.

PubMed

Mar, Javier; Arrospide, Arantzazu; Comas, Mercè

2010-01-01

Thrombolysis within the first 3 hours after the onset of symptoms of a stroke has been shown to be a cost-effective treatment because treated patients are 30% more likely than nontreated patients to have no residual disability. The objective of this study was to calculate by means of a discrete event simulation model the budget impact of thrombolysis in Spain. The budget impact analysis was based on stroke incidence rates and the estimation of the prevalence of stroke-related disability in Spain and its translation to hospital and social costs. A discrete event simulation model was constructed to represent the flow of patients with stroke in Spain. If 10% of patients with stroke from 2000 to 2015 would receive thrombolytic treatment, the prevalence of dependent patients in 2015 would decrease from 149,953 to 145,922. For the first 6 years, the cost of intervention would surpass the savings. Nevertheless, the number of cases in which patient dependency was avoided would steadily increase, and after 2006 the cost savings would be greater, with a widening difference between the cost of intervention and the cost of nonintervention, until 2015. The impact of thrombolysis on society's health and social budget indicates a net benefit after 6 years, and the improvement in health grows continuously. The validation of the model demonstrates the adequacy of the discrete event simulation approach in representing the epidemiology of stroke to calculate the budget impact.

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.

Thrombolysis for stroke in pregnancy at 39 weeks gestation with a subsequent normal delivery.

PubMed

Ritchie, Joanne; Lokman, Mariam; Panikkar, Jane

2015-08-11

Stroke during pregnancy is fortunately a rare event, however, it can have severe consequences, with 9.5% of all maternal deaths being related to stroke. The most common presentation is an ischaemic stroke. There has been much debate as to the correct treatment for such cases' and whether thrombolysis can be used safely in pregnancy. Our case describes a 28-year-old woman with a previous normal vaginal delivery presenting in her third trimester with a sudden onset of dense left hemiparesis. She was successfully treated with alteplase, an intravenous recombinant tissue-type plasminogen activator, and made a full recovery after normal delivery of a healthy infant. This case report highlights one of the first documented successful outcomes from thrombolysis for this condition in the UK and may help inform future management of these women. 2015 BMJ Publishing Group Ltd.

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.

Evaluation of high resolution ultrasound as a tool for assessing the 3D volume of blood clots during in vitro thrombolysis.

PubMed

Auboire, Laurent; Escoffre, Jean-Michel; Fouan, Damien; Jacquet, Jean-René; Ossant, Frédéric; Grégoire, Jean-Marc; Bouakaz, Ayache

2017-07-24

Thrombosis is a major cause of several diseases, i.e. myocardial infarction, cerebral stroke and pulmonary embolism. Thrombolytic therapies are required to induce fast and efficient recanalization of occluded vessels. To evaluate the in vitro efficacy of these thrombolytic strategies, measuring clot dissolution is essential. This study aimed to evaluate and validate high resolution ultrasound as a tool to assess the exact volume of clots in 3D and in real time during in vitro thrombolytic drug testing. This new method was validated by measuring the effects of concentration range of recombinant tissue type plasminogen activator on a blood clot during complete occlusion or 70% stenosis of a vessel. This study shows that high resolution ultrasound imaging allows for a real-time assessment of the 3D volume of a blood clot with negligible inter- and intra-operator variabilities. The conclusions drawn from this study demonstrate the promising potential of high resolution ultrasound imaging for the in vitro assessment of new thrombolytic drugs.

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.

Electrocardiogram interpretation in general practice: relevance to prehospital thrombolysis.

PubMed Central

McCrea, W A; Saltissi, S

1993-01-01

OBJECTIVE--To assess, in the context of their possible role in prehospital thrombolysis, the ability of general practitioners to recognise acute transmural myocardial ischaemia/infarction on an electrocardiogram. DESIGN--150 doctors (every fifth name) were selected from the alphabetical list of 750 on Merseyside general practitioner register and without prior warning were asked to interpret a series of six 12 lead electrocardiograms. Three of these showed acute transmural ischaemia/infarction, one was normal, and two showed non-acute abnormalities. Details of doctors' ages, postgraduate training, and clinical practice were sought. SETTING--General practitioners' surgeries and postgraduate centres within the Merseyside area. PARTICIPANTS--106 general practitioners (mean age 45 years) agreed to participate. MAIN OUTCOME MEASURE--Accuracy of general practitioners' interpretations of the six electrocardiograms. RESULTS--82% of general practitioners correctly recognised a normal electrocardiogram. Recognition of acute abnormalities was less reliable. Between 33% and 61% correctly identified acute transmural ischaemia/infarction depending on the specific trace presented. Accurate localisation of the site of the infarct was achieved only by between 8% and 30% of participants, while between 22% and 25% correctly interpreted non-acute abnormalities. Neither routine use of electrocardiography nor postgraduate hospital experience in general medicine was associated with significantly greater expertise. CONCLUSION--The current level of proficiency of a sample of general practitioners in the Merseyside area in recognising acute transmural ischaemia/infarction on an electrocardiogram suggests that refresher training is needed if general practitioners are to give prehospital thrombolysis. Images PMID:8398491

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.

Ultrasound guided V3 segment vertebral artery direct percutaneous puncture for basilar artery mechanical thrombectomy in acute stroke: a technical report.

PubMed

Desai, Jamsheed A; Almekhlafi, Mohammed A; Hill, Michael D; Goyal, Mayank; Eesa, Muneer

2014-04-01

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.

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.

Process improvement to enhance existing stroke team activity toward more timely thrombolytic treatment.

PubMed

Cho, Han-Jin; Lee, Kyung Yul; Nam, Hyo Suk; Kim, Young Dae; Song, Tae-Jin; Jung, Yo Han; Choi, Hye-Yeon; Heo, Ji Hoe

2014-10-01

Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process. After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared. The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]. PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

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.

Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

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

Yang, Shuofei, E-mail: yangshuofei@gmail.com; Liu, Baochen, E-mail: 306446264@qq.com; Ding, Weiwei, E-mail: dingwei-nju@hotmail.com

PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement inmore » symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.« less

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.

The metabolic syndrome is associated with a higher resistance to intravenous thrombolysis for acute ischemic stroke in women than in men.

PubMed

Arenillas, Juan F; Sandoval, Patricio; Pérez de la Ossa, Natalia; Millán, Mónica; Guerrero, Cristina; Escudero, Domingo; Dorado, Laura; López-Cancio, Elena; Castillo, José; Dávalos, Antoni

2009-02-01

The metabolic syndrome (MetS) might confer a higher resistance to intravenous thrombolysis in acute middle cerebral artery (MCA) ischemic stroke. MetS increases the risk of stroke in women to a greater extent than in men. We aimed to investigate whether there might be sex differences in the impact of MetS on the response to intravenous thrombolysis for acute MCA ischemic stroke. We prospectively studied consecutive ischemic stroke patients, treated with intravenous tissue-type plasminogen activator according to SITS-MOST criteria, with an MCA occlusion on prebolus transcranial Doppler examination. Resistance to thrombolysis was defined as the absence of complete MCA recanalization 24 hours after tissue-type plasminogen activator infusion by transcranial Doppler criteria. MetS was diagnosed according to the criteria established by the American Heart Association/National Heart, Lung, and Blood Institute 2005 statement. A total of 125 patients (75 men, 50 women; mean age, 67.6+/-11 years) were included. MetS was diagnosed in 76 (61%) patients. Resistance to clot lysis at 24 hours was observed in 53 (42%) patients. Two multivariate-adjusted, logistic-regression models identified that MetS was associated with a higher resistance to tissue-type plasminogen activator, independently of other significant baseline variables (odds ratio=9.8; 95% CI, 3.5 to 27.8; P=0.0001) and of the individual components of the MetS. The MetS was associated with a significantly higher odds of resistance to thrombolysis in women (odds ratio=17.5; 95% CI, 1.9 to 163.1) than in men (odds ratio=5.1; 95% CI, 1.6 to 15.6; P for interaction=0.0004). The effect of MetS on the resistance to intravenous thrombolysis for acute MCA ischemic stroke appears to be more pronounced in women than in men.

Cortical myoclonus during IV thrombolysis for ischemic stroke

PubMed Central

Bentes, Carla; Peralta, Rita; Viana, Pedro; Morgado, Carlos; Melo, Teresa P.; Ferro, José M.

2014-01-01

We describe a patient with an acute middle cerebral artery ischemic stroke developing subtle involuntary movements of the paretic upper limb with cortical origin during rt-PA perfusion. Despite the multiple potential pathophysiological mechanisms for the relationship between thrombolysis and epileptic activity, seizures during this procedure are scarcely reported. Our hypothesis is that subtle and transient clinical seizures, like those described in our patient, may not be detected or are misdiagnosed as nonepileptic involuntary movements. We aimed to draw attention to the recognition challenge of this paroxysmal motor behavior, highlighting this clinical and neurophysiological identification using video recording and back-average analysis of the EEG. PMID:25667903

Reperfusion of occluded branch retinal arteries by transluminal Nd:YAG laser embolysis combined with intravenous thrombolysis of urokinase

PubMed Central

Chai, Fang; Du, Shanshuang; Zhao, Xiquan

2017-01-01

Purpose: To report successful treatment with transluminal Nd:YAG laser embolysis (TYE) combined with urokinase thrombolysis for reperfusion of occluded branch retinal arteries with visible emboli. Methods: A total of 34 eyes from 34 patients with acute, severe vision loss secondary to a branch retinal artery occlusion with visible emboli and retinal whitening were examined. Each patient was administered TYE therapy, which focused on the embolus, using an ocular contact lens; a 0.3–0.9 mJ laser pulse was delivered directly and gradually according to the reaction. Fundus photographs and fundus fluorescein angiography (FFA) were obtained before and immediately after the laser treatment. All patients received urokinase thrombolysis therapy drops intravenously for 5 days at 10–20 u/d. The follow-up period ranged from 6 to 14 months after therapy. The morphological characteristics of FFA associated with obstruction recovery of arterial fluorescence filling and visual function were analyzed. Results: After TYE therapy, FFA examinations showed that the retinal artery and its branches exhibited completely restored blood flow without obstruction in 13 eyes, accounting for 38.2% of the cases. The blood flow was mostly recovered in 11 eyes (32.4% of patients). FFA examinations following the combined intravenous urokinase thrombolysis therapy showed that the retinal artery and its branches exhibited completely restored blood flow after obstruction in 16 eyes (47.1% of patients). The blood flow was mostly recovered in 15 eyes (44.1% of patients). Conclusion: TYE combined with urokinase thrombolysis is effective for reperfusion of occluded branch retinal arteries and improving visual recovery in patients with visible emboli. PMID:29162667

MRI based thrombolysis for FLAIR-negative stroke patients within 4.5-6h after symptom onset.

PubMed

Wei, Xiao-Er; Zhou, Jia; Li, Wen-Bin; Zhao, Yu-Wu; Li, Ming-Hua; Li, Yue-Hua

2017-01-15

To investigate the feasibility of DWI-FLAIR mismatch in identifying patients who might benefit from thrombolytic therapy within 4.5-6h, we analyzed the data of 105 ischemic stroke patients with known time of symptom onset who underwent MRI within 6h of stroke and thrombolysis between December 2006 and December 2013. They were divided into three groups: symptom onset within 4.5h (n=66); 4.5-6h and FLAIR images negative (n=9); and 4.5-6h and FLAIR images positive (n=30). Outcome of thrombolysis was assessed for each group by recanalization rate, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. The results showed that mismatch between positive DWI and negative FLAIR images identified patients within 4.5h of symptom onset with sensitivity, specificity, positive predictive value and negative predictive value of 40.9%, 76.9%, and 75% and 43.5%. Recanalization rate, NIHSS score and mRS score were all better in both the 0-4.5h and 4.5-6h FLAIR-negative groups than in the 4.5-6h FLAIR-positive group (p<0.05). These data demonstrate that within 4.5-6h of symptom onset, patients with negative FLAIR images may benefit from thrombolysis therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

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

TREATMENT OF MICROVASCULAR MICRO-EMBOLIZATION USING MICROBUBBLES AND LONG-TONE-BURST ULTRASOUND: AN IN VIVO STUDY

PubMed Central

Pacella, John J.; Brands, Judith; Schnatz, Frederick G.; Black, John J.; Chen, Xucai; Villanueva, Flordeliza S.

2015-01-01

Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction

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.

Collaborative Interventions Reduce Time-to-Thrombolysis for Acute Ischemic Stroke in a Public Safety Net Hospital.

PubMed

Threlkeld, Zachary D; Kozak, Benjamin; McCoy, David; Cole, Sara; Martin, Christine; Singh, Vineeta

2017-07-01

Shorter time-to-thrombolysis in acute ischemic stroke (AIS) is associated with improved functional outcome and reduced morbidity. We evaluate the effect of several interventions to reduce time-to-thrombolysis at an urban, public safety net hospital. All patients treated with tissue plasminogen activator for AIS at our institution between 2008 and 2015 were included in a retrospective analysis of door-to-needle (DTN) time and associated factors. Between 2011 and 2014, we implemented 11 distinct interventions to reduce DTN time. Here, we assess the relative impact of each intervention on DTN time. The median DTN time pre- and postintervention decreased from 87 (interquartile range: 68-109) minutes to 49 (interquartile range: 39-63) minutes. The reduction was comprised primarily of a decrease in median time from computed tomography scan order to interpretation. The goal DTN time of 60 minutes or less was achieved in 9% (95% confidence interval: 5%-22%) of cases preintervention, compared with 70% (58%-81%) postintervention. Interventions with the greatest impact on DTN time included the implementation of a stroke group paging system, dedicated emergency department stroke pharmacists, and the development of a stroke code supply box. Multidisciplinary, collaborative interventions are associated with a significant and substantial reduction in time-to-thrombolysis. Such targeted interventions are efficient and achievable in resource-limited settings, where they are most needed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

The Risk of Hemorrhagic Transformation After Thrombolysis for Acute Ischemic Stroke in Chinese Versus North Americans: A Comparative Study.

PubMed

Xu, Xiaomeng; Wang, Deren; Wang, Fang; Norton, Casey; Liu, Xinfeng; Selim, Magdy

2018-05-16

There is a widespread belief that Asians are more susceptible to hemorrhagic transformation (HT) after receiving recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke (AIS). However, this has not been examined in clinical practice. This study aims to compare the incidence of symptomatic hemorrhagic transformation (SHT) among thrombolysis-treated AIS patients in China and in the United States. We compared 212 consecutive patients receiving thrombolysis within 4.5 hours of onset ± endovascular therapy from an American (n = 86) and a Chinese Stroke Center (n = 126). SHT was defined using various definitions based on the National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (NINDS rt-PA) trials, European-Australian Cooperative Acute Stroke Study 2 (ECASS2), and a modified version of Safe Implementation of Thrombolysis in Stroke-Monitoring Study (mSITS-MOST) study criteria. We used Firth logistic regression to adjust for confounding variables and to identify potential predictors. American patients were older, and had higher prevalence of diabetes, hypertension, cardiac disease, and prestroke use of antithrombotics. They also had higher baseline serum glucose, shorter onset-to-treatment time, and fewer endovascular treatments. The rates of SHT were higher in the American cohort compared to the Chinese cohort: 18.6% versus 14.3% based on NINDS definition of SHT; 15.1% versus 12.7% based on ECASS2; and 11.6% versus 7.2% based on mSITS-MOST. However, none of these differences were significant (unadjusted and adjusted P values > .05). Fatal HT was comparable in Americans versus Chinese (8.1% versus 8.7%). Serum glucose emerged as an independent predictor of SHT (P = .024). In our cohorts, the rate of SHT after thrombolysis is equivalent between Chinese and North American stroke patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical-Radiological Parameters Improve the Prediction of the Thrombolysis Time Window by Both MRI Signal Intensities and DWI-FLAIR Mismatch.

PubMed

Madai, Vince Istvan; Wood, Carla N; Galinovic, Ivana; Grittner, Ulrike; Piper, Sophie K; Revankar, Gajanan S; Martin, Steve Z; Zaro-Weber, Olivier; Moeller-Hartmann, Walter; von Samson-Himmelstjerna, Federico C; Heiss, Wolf-Dieter; Ebinger, Martin; Fiebach, Jochen B; Sobesky, Jan

2016-01-01

With regard to acute stroke, patients with unknown time from stroke onset are not eligible for thrombolysis. Quantitative diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) MRI relative signal intensity (rSI) biomarkers have been introduced to predict eligibility for thrombolysis, but have shown heterogeneous results in the past. In the present work, we investigated whether the inclusion of easily obtainable clinical-radiological parameters would improve the prediction of the thrombolysis time window by rSIs and compared their performance to the visual DWI-FLAIR mismatch. In a retrospective study, patients from 2 centers with proven stroke with onset <12 h were included. The DWI lesion was segmented and overlaid on ADC and FLAIR images. rSI mean and SD, were calculated as follows: (mean ROI value/mean value of the unaffected hemisphere). Additionally, the visual DWI-FLAIR mismatch was evaluated. Prediction of the thrombolysis time window was evaluated by the area-under-the-curve (AUC) derived from receiver operating characteristic (ROC) curve analysis. Factors such as the association of age, National Institutes of Health Stroke Scale, MRI field strength, lesion size, vessel occlusion and Wahlund-Score with rSI were investigated and the models were adjusted and stratified accordingly. In 82 patients, the unadjusted rSI measures DWI-mean and -SD showed the highest AUCs (AUC 0.86-0.87). Adjustment for clinical-radiological covariates significantly improved the performance of FLAIR-mean (0.91) and DWI-SD (0.91). The best prediction results based on the AUC were found for the final stratified and adjusted models of DWI-SD (0.94) and FLAIR-mean (0.96) and a multivariable DWI-FLAIR model (0.95). The adjusted visual DWI-FLAIR mismatch did not perform in a significantly worse manner (0.89). ADC-rSIs showed fair performance in all models. Quantitative DWI and FLAIR MRI biomarkers as well as the visual DWI-FLAIR mismatch provide excellent

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

The t-PA-encapsulated PLGA nanoparticles shelled with CS or CS-GRGD alter both permeation through and dissolving patterns of blood clots compared with t-PA solution: an in vitro thrombolysis study.

PubMed

Wang, Shoei-Shen; Chou, Nai-Kuan; Chung, Tze-Wen

2009-12-01

Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 mum, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 mum. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. Copyright 2008 Wiley Periodicals, Inc.

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.

Influence of arterial occlusion on outcome after intravenous thrombolysis for acute ischemic stroke.

PubMed

Medlin, Friedrich; Amiguet, Michael; Vanacker, Peter; Michel, Patrik

2015-01-01

We aimed to assess the interaction between intravenous thrombolysis (IVT) and arterial occlusion on acute cervicocerebral computed tomographic angiography on the outcome of patients with acute ischemic stroke. Patients from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry with onset-to-door-time ≤4 hours, acute cervicocerebral computed tomographic angiography, a premorbid modified Rankin Scale ≤2, and a National Institute of Health Stroke Scale (NIHSS) >4 were selected. Patients with significant intracranial arterial obstruction (≥50%-99%) and undergoing acute endovascular treatment were excluded. An interaction analysis of IVT and initial arterial occlusion for favorable 3 months outcome (modified Rankin Scale <3) were performed with adjustment for potential confounders. Among 654 included patients, 382 (58%) showed arterial occlusion, of whom 263 (69%) received IVT. Two hundred seventy-two showed no/minimal obstruction of whom 139 (51%) received IVT. In the adjusted interaction analysis, there was a trend in favor of the arterial occlusion group (odds ratio [OR]=3.97; 95% confidence interval [CI], 0.83-18.97; P=0.08). IVT (versus no IVT) was associated with better outcome in patients with occlusion (adjusted OR for favorable outcome, 3.01; 95% CI, 1.10-8.28) but not in patients with no/minimal obstruction (OR, 0.76; 95% CI, 0.21-2.74). Conversely, patients with occlusion had a similar rate of favorable outcome as no/minimal obstruction when thrombolysed (OR, 0.5; 95% CI, 0.17-1.47) but had a less favorable outcome without thrombolysis (OR, 0.13; 95% CI, 0.04-0.44). In this retrospective analysis of consecutive patients with acute ischemic stroke, there was a trend for more favorable outcomes with IVT in the setting of initial arterial occlusion than in the setting of no/minimal obstruction. Before confirmation in randomized controlled studies, this information should not influence thrombolysis decisions, however. © 2014 American Heart

Twelve-month experience of acute stroke thrombolysis in Christchurch, New Zealand: emergency department screening and acute stroke service treatment.

PubMed

Fink, John

2005-05-06

To determine the safety and efficiency of an acute stroke thrombolysis service in a New Zealand public hospital setting. A 12-month audit of patients referred to the Christchurch Hospital Stroke Thrombolysis Service (STS) between 1 April 2002 and 31 March 2003 was undertaken. Sixty-one patients were referred to the STS during the study period, of whom 16 were treated with tissue plasminogen activator (t-PA). For treated patients, the median time from stroke onset to hospital presentation was 60 minutes, 'door-to-CT' time was 60 minutes, and the 'door-to-needle' time was 99 minutes. Minor protocol violations were recorded in two patients, but did not influence outcome. No patient was treated after 3 hours of stroke onset. Intracerebral haemorrhage occurred in two patients: one patient was significantly improved compared with pre-treatment status; a minor temporary deterioration occurred in the other patient. Eight of 16 patients had improved by 4 or more points on the NIH Stroke Scale Score at 24 hours. Acute stroke thrombolysis can be delivered safely and in accordance with internationally accepted guidelines using the Christchurch Hospital STS model of emergency department screening and acute stroke service treatment. Further improvements in performance of the STS remain possible.

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

Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro, and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia.

PubMed

Chazalviel, Laurent; Haelewyn, Benoit; Degoulet, Mickael; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

2016-01-01

Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro , and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo . In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

Validation of minor stroke definitions for thrombolysis decision making.

PubMed

Park, Tai Hwan; Hong, Keun-Sik; Choi, Jay Chol; Song, Pamela; Lee, Ji Sung; Lee, Juneyoung; Park, Jong-Moo; Kang, Kyusik; Lee, Kyung Bok; Cho, Yong-Jin; Saposnik, Gustavo; Han, Moon-Ku; Bae, Hee-Joon

2013-05-01

Patients with low National Institutes of Health Stroke Scale (NIHSS) scores are frequently excluded from thrombolysis, but more than 25% of them remain disabled. We sought to define a validated minor stroke definition to reduce the inappropriate treatment exclusion. From an outcome database, untreated patients with an NIHSS score of 5 or less presenting within a 4.5-hour window were identified and 3-month modified Rankin Scale (mRS) outcomes were analyzed according to individual isolated symptoms and total NIHSS scores. The validity of the following minor stroke definitions were assessed: (1) the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator (NINDS-TPA) trials' definition, (2) the total NIHSS score, varying a cutoff point from 0 to 4, and (3) our proposed definition that included an NIHSS score = 0 or an NIHSS score = 1 on the items of level of consciousness (LOC), gaze, facial palsy, sensory, or dysarthria. Of 647 patients, 172 patients (26.6%) had a 3-month unfavorable outcome (mRS score 2-6). Favorable outcome was achieved in more than 80% of patients with an NIHSS score of 1 or less or with an isolated symptom on the LOC, gaze, facial palsy, sensory, or dysarthria item. In contrast, unfavorable outcome proportion was more than 25% in patients with an NIHSS score of 2 or more. When the NINDS-TPA trials' definition, our definition, or the definition of an NIHSS score of 1 or less were applied, more than 75% of patients with an unfavorable outcome were defined as a non-minor stroke and less than 15% of patients with an unfavorable outcome were defined as a minor stroke. Implementation of an optimal definition of minor stroke into thrombolysis decision-making process would decrease the unfavorable outcomes in patients with low NIHSS scores. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

PubMed

Calleja, A I; Cortijo, E; García-Bermejo, P; Gómez, R D; Pérez-Fernández, S; Del Monte, J M; Muñoz, M F; Fernández-Herranz, R; Arenillas, J F

2013-05-01

Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Construction of polylysine dendrimer nanocomposites carrying nattokinase and their application in thrombolysis.

PubMed

Wu, Can; Gao, Chunmei; Lü, Shaoyu; Xu, Xiubin; Wen, Na; Zhang, Shaofei; Liu, Mingzhu

2018-02-01

Thrombotic disease has become one of the leading causes of mortality among humans globally. Nattokinase (NK), a novel thrombolytic agent, has attracted the attention of researchers. However, NK is a serine protease that is vulnerable to environmental effects resulting in its inactivation. In this study, polylysine dendrimer (PLLD) was synthesized through divergence-convergence method, and a series of NK/PLLD nanocomposites with different molar ratio was prepared. In addition, NK was successfully incorporated into the cores of PLLD G4 through hydrogen bonds and van der Waals forces. In NK/PLLD nanocomposites, when the molar ratio of NK to PLLD is 1:30, a high relative enzyme activity level (up to 117%) was achieved and was more stable at different temperatures and pH than free NK. In in vitro thrombolysis experiment, compared with free NK, NK/PLLD nanocomposites could control the release of NK. The thrombolysis rate of NK/PLLD nanocomposites reached 50% at 12 h, which can effectively avoid other complications such as hemorrhage. Interestingly, NK/PLLD nanocomposites with positive charge can penetrate into the negatively charged thrombus through electrostatic interaction, thus providing a good thrombolytic effect. Hemolysis and MTT experiments show that PLLD nanomaterials can serve as ideal carriers of protein drugs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 440-449, 2018. © 2017 Wiley Periodicals, Inc.

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

Leukoaraiosis, cerebral hemorrhage and outcome after IV thrombolysis for acute ischemic stroke: A meta-analysis (v1)

PubMed Central

Charidimou, Andreas; Pasi, Marco; Fiorelli, Marco; Shams, Sara; von Kummer, Rüdiger; Pantoni, Leonardo; Rost, Natalia

2016-01-01

Background-and-Purpose We performed a meta-analysis to assess whether leukoaraiosis on brain CT scans of acute ischemic stroke patients treated with intravenous (IV) thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) and/or poor functional outcome at 3–6 months post-stroke. Methods We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3–6 month modified Rankin Score (mRS) >2. Results Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR: 1.55; 95%CI: 1.17–2.06, p=0.002) and severe leukoaraiosis (OR: 2.53; 95%CI: 1.92–3.34, p<0.0001), compared to patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in six included studies (n=4976, adjusted-OR: 1.75, 95%CI: 1.35–2.27; p<0.0001). OR for leukoaraiosis and poor 3–6 month outcome was 2.02 (95%CI: 1.54–2.65, p<0.0001), with significant statistical heterogeneity (I2:75.7%, p=0.002). In adjusted analysed, leukoaraiosis was an independent predictor of poor outcome (n=3688, adjusted-OR: 1.61, 95%CI: 1.44–1.79; p<0.0001). In post-hoc analyses, including only leukoaraiosis patients in RCTs (IST-3, NINDS, ECASS-1-2; n=2234), tPA vs. control was associated with higher sICH risk (OR: 5.50; 95%CI: 2.49–12.13), but lower poor outcome risk (OR: 0.75; 95%CI: 0.60–0.95). Conclusions Leukoaraiosis might increase post-IV thrombolysis sICH risk and poor outcome post-stroke. Despite increased sICH risk, IV tPA treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding IV thrombolysis. PMID:27491738

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.

AToMS: A Ubiquitous Teleconsultation System for Supporting AMI Patients with Prehospital Thrombolysis.

PubMed

Correa, Bruno S P M; Gonçalves, Bernardo; Teixeira, Iuri M; Gomes, Antônio T A; Ziviani, Artur

2011-01-01

The latest population-based studies in the medical literature worldwide indicate that acute myocardial infarction (AMI) patients still experience prolonged delay to be rescued, which often results in morbidity and mortality. This paper reports from a technological standpoint a teleconsultation and monitoring system named AToMS. This system addresses the problem of prehospital delivery of thrombolysis to AMI patients by enabling the remote interaction of the paramedics and a cardiologist available at a Coronary Care Unit (CCU). Such interaction allows the diagnosis of the patient eligibility to the immediate application of thrombolysis, which is meant to reduce the delay between the onset of symptoms and the eventual application of proper treatment. Such delay reduction is meant to increase the AMI patient's chances of survival and decrease the risks of postinfarction sequels. The teleconsultation is held with the support of wireless and mobile technologies, which also allows the cardiologist to monitor the patient while he/she is being taken to the nearest CCU. All exchanged messages among paramedics and cardiologists are recorded to render an auditable system. AToMS has been deployed in a first stage in the city of Rio de Janeiro, where the medical team involved in the project has conducted commissioned tests.

NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.

PubMed

Nacu, Aliona; Kvistad, Christopher E; Naess, Halvor; Øygarden, Halvor; Logallo, Nicola; Assmus, Jörg; Waje-Andreassen, Ulrike; Kurz, Kathinka D; Neckelmann, Gesche; Thomassen, Lars

2017-02-01

The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961. © 2016 The Authors.

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.

In vitro thrombolytic efficacy of echogenic liposomes loaded with tissue plasminogen activator and octafluoropropane gas

NASA Astrophysics Data System (ADS)

Shekhar, Himanshu; Bader, Kenneth B.; Huang, Shenwen; Peng, Tao; Huang, Shaoling; McPherson, David D.; Holland, Christy K.

2017-01-01

Echogenic liposomes loaded with the thrombolytic recombinant tissue-type plasminogen activator (rt-PA) are under development for the treatment of ischemic stroke. These agents are designed to co-encapsulate cavitation nuclei to promote bubble activity in response to ultrasound exposure, and to enable localized delivery of thrombolytic. Stable cavitation improves the efficacy of the thrombolytic through enhanced fluid mixing. Echogenic liposomes that encapsulate air-filled microbubbles nucleate scant stable cavitation activity in response to 120 kHz intermittent ultrasound exposure, and have demonstrated thrombolytic efficacy equivalent to rt-PA alone. It was hypothesized that encapsulating octafluoropropane (OFP) gas within rt-PA-loaded liposomes instead of air will enhance ultrasound-mediated stable cavitation activity and increase thrombolytic efficacy compared to previous studies. The thrombolytic efficacy and cavitation activity nucleated from liposomes that encapsulate OFP microbubbles and rt-PA (OFP t-ELIP) was evaluated in vitro. Human whole blood clots were exposed to human fresh-frozen plasma alone, rt-PA (0, 0.32, 1.58, and 3.15 µg ml-1), or OFP t-ELIP at equivalent enzymatic activity, with and without exposure to intermittent ultrasound. Further, numerical simulations were performed to gain insight into the mechanisms of cavitation nucleation. Sustained ultraharmonic activity was nucleated from OFP t-ELIP when exposed to ultrasound. Furthermore, the thrombolytic efficacy was enhanced compared to rt-PA alone at concentrations of 1.58 µg ml-1 and 3.15 µg ml-1 (p  <  0.05). These results indicate that OFP t-ELIP can nucleate sustained stable cavitation activity and enhance the efficacy of thrombolysis.

Digestive and urologic hemorrhage after intravenous thrombolysis for acute ischemic stroke: Data from a Chinese stroke center.

PubMed

Chang, Hong; Wang, Xiaojuan; Yang, Xin; Song, Haiqing; Qiao, Yuchen; Liu, Jia

2017-02-01

Objective Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is considered the most effective treatment method for AIS; however, it is associated with a risk of hemorrhage. We analyzed the risk factors for digestive and urologic hemorrhage during rt-PA therapy. Methods We retrospectively analyzed patients with AIS who underwent intravenous thrombolysis with rt-PA during a 5-year period in a Chinese stroke center. Data on the demographics, medical history, laboratory test results, and clinical outcomes were collected. Results 338 patients with AIS were eligible and included. Logistic regression multivariate analysis showed that gastric catheter was significantly correlated with digestive hemorrhage, while age and urinary catheter were significantly correlated with urologic hemorrhage. Most hemorrhagic events were associated with catheterization after 1 to 24 hours of rt-PA therapy. Conclusions In summary, gastric and urinary catheters were correlated with digestive and urologic hemorrhage in patients with AIS undergoing rt-PA therapy. Well-designed controlled studies with large samples are required to confirm our findings.

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; ...

In vivo Sonothrombolysis of Ear Marginal Vein of Rabbits Monitored with High-frequency Ultrasound Needle Transducer.

PubMed

Chen, Ruimin; Paeng, Dong-Guk; Lam, Kwok Ho; Zhou, Qifa; Shung, K Kirk; Matsuoka, Naoki; Humayun, Mark S

2013-01-01

Ultrasound (US) is known to enhance thrombolysis when thrombolytic agents and/or microbubbles are injected into the targeted vessels. In this research, high-intensity US (1 MHz, 7 W/cm 2 , 30 % duty cycle) was applied in vivo to the ear marginal vein of three rabbits which was occluded by either laser photothrombosis or thrombin, right after the injection of 0.3~0.6 cc of microbubbles (13 × 10 8 bubbles/ml of concentration) through the other ear vein without using any thrombolytic agent. To determine the effect of the sonothrombolysis, the blood flow velocity near the occlusion site in the vein was measured by a custom-made 40-MHz US needle transducer and its corresponding Doppler US system. The Doppler spectra show that the blood flow velocity recovered from total occlusion after three 10-minute high-intensity US treatments. Fluorescein angiography was employed to confirm the opening of the vessel occlusion. A control study of three rabbits with only the microbubble injection showed no recovery on the occlusion in 3 hours. The results show that the sonothrombolysis in the rabbit ear marginal vein can be achieved with microbubbles only. The results of cavitation measurements indicate that the mechanism of sonothrombolysis is probably due to the cavitation induced by the microbubbles. Without the need of applying any thrombolytic agent, high-intensity US has high potential for therapies targeting on small blood vessels.

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.

Surgical Access to Jejunal Veins for Local Thrombolysis and Stent Placement in Portal Vein Thrombosis

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

Schellhammer, Frank, E-mail: frank.schellhammer@med.uni-duesseldorf.d; Esch, Jan Schulte am; Hammerschlag, Sascha

2008-07-15

Portal vein thrombosis is an infrequent entity, which may cause high morbidity and mortality. We report a case of portal vein thrombosis due to benign stenosis following partial pancreatoduodenectomy with segmental replacement of the portal vein by a Gore-tex graft. Using a surgical access to jenunal veins, local thrombolysis, mechanical fragmentation of thrombus, and stent placement were successfully performed.

Does the 'diffusion of innovations' model enrich understanding of research use? Case studies of the implementation of thrombolysis services for stroke.

PubMed

Boaz, Annette; Baeza, Juan; Fraser, Alec

2016-10-01

To test whether the model of 'diffusion of innovations' enriches understanding of the implementation of evidence-based thrombolysis services for stroke patients. Four case studies of the implementation of evidence on thrombolysis in stroke services in England and Sweden. Semistructured interviews with 95 staff including doctors, nurses and managers working in stroke units, emergency medicine, radiology, the ambulance service, community rehabilitation services and commissioners. The implementation of thrombolysis in acute stroke management benefited from a critical mass of the factors featured in the model including: the support of national and local opinion leaders; a strong evidence base and financial incentives. However, while the model provided a starting point as an organizational framework for mapping the critical factors influencing implementation, to understand properly the process of implementation and the importance of the different factors identified, more detailed analyses of context and, in particular, of the human and social dimensions of change was needed. While recognising the usefulness of the model of diffusion of innovations in mapping the processes by which diffusion occurs, the use of methods that lend themselves to in-depth analysis, such as ethnography and the application of relevant bodies of social theory, are needed. © The Author(s) 2016.

Anatomic and functional outcomes of pharmacomechanical and catheter-directed thrombolysis of iliofemoral deep venous thrombosis.

PubMed

Hager, Eric; Yuo, Theodore; Avgerinos, Efthymios; Naddaf, Abdullah; Jeyabalan, Geetha; Marone, Luke; Chaer, Rabih

2014-07-01

Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are commonly used for the treatment of iliofemoral deep venous thrombosis (DVT). The purpose of this study was to examine the short- and long-term venous patency and venous valvular function as well as clinical outcomes of patients treated for iliofemoral DVT by PMT and CDT. A retrospective review of all patients with symptomatic DVT treated between 2006 and 2011 with PMT or CDT was performed. All patients were treated by local tissue plasminogen activator delivered with PMT or CDT. Patients were divided into two groups on the basis of initial treatment modality: patients treated by PMT alone (group 1), and those who underwent PMT and CDT or CDT alone (group 2). Group comorbidities, initial presenting symptoms, and Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification scores were compared. Postprocedural duplex ultrasound was used to assess valve function and treated vein patency rates. At all visits, Villalta and CEAP scores were recorded and compared. Group demographic and procedural results were analyzed by Fisher exact test for dichotomous variables and Kruskal-Wallis equality-of-populations rank test for the ordinal and continuous data. Kaplan-Meier survival estimates were used to assess preserved valve function as well as primary and secondary patency rates. There were 79 patients with 102 limbs treated for extensive iliofemoral DVT (median age, 51.5 years; range, 16.6-83.8 years). There were 18 patients in group 1 and 61 patients in group 2 (PMT + CDT [n = 54] or CDT alone [n = 7]). There were no differences in demographics or comorbidities between groups aside from malignant disease, which was more common in group 1 (35.3% vs 11.5%; P = .03). A total of 102 limbs were analyzed, 24 in group 1 and 78 in group 2. Patients in group 1 had a shorter symptom duration compared with group 2 (7 days vs 16 days; P = .011). The median number of procedures in group 1

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.

Acousto-mechanical and thermal properties of clotted blooda)

PubMed Central

Nahirnyak, Volodymyr M.; Yoon, Suk Wang; Holland, Christy K.

2007-01-01

The efficacy of ultrasound-assisted thrombolysis as an adjunct treatment of ischemic stroke is being widely investigated. To determine the role of ultrasound hyperthermia in the process of blood clot disruption, the acousto-mechanical and thermal properties of clotted blood were measured in vitro, namely, density, speed of sound, frequency-dependent attenuation, specific heat, and thermal conductivity. The amplitude coefficient of attenuation of the clots was determined for 120 kHz, 1.0 MHz, and 3.5 MHz ultrasound at room temperature (20±2 °C). The attenuation coefficient ranged from 0.10 to 0.30 Np/cm in porcine clots and from 0.09 to 0.23 Np/cm in human clots. The experimentally determined values of specific heat and thermal conductivity for porcine clotted blood are (3.2±0.5)×103 J/kg·K and 0.55±0.13 W/m·K, respectively, and for human clotted blood are (3.5±0.8)×103 J/kg·K and 0.59±0.11 W/m·K, respectively. Measurements of the acousto-mechanical and thermal properties of clotted blood can be helpful in theoretical modeling of ultrasound hyperthermia in ultrasound-assisted thrombolysis and other high-intensity focused ultrasound applications. PMID:16838520

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.

Validation of the DRAGON Score in a Chinese Population to Predict Functional Outcome of Intravenous Thrombolysis-Treated Stroke Patients.

PubMed

Zhang, Xinmiao; Liao, Xiaoling; Wang, Chunjuan; Liu, Liping; Wang, Chunxue; Zhao, Xingquan; Pan, Yuesong; Wang, Yilong; Wang, Yongjun

2015-08-01

The DRAGON score predicts functional outcome of ischemic stroke patients treated with intravenous thrombolysis. Our aim was to evaluate its utility in a Chinese stroke population. Patients with acute ischemic stroke treated with intravenous thrombolysis were prospectively registered in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China. We excluded patients with basilar artery occlusion and missing data, leaving 970 eligible patients. We calculated the DRAGON score, and the clinical outcome was measured by the modified Rankin Scale at 3 months. Model discrimination was quantified by calculating the C statistic. Calibration was assessed using Pearson correlation coefficient. The C statistic was .73 (.70-.76) for good outcome and .75 (.70-.79) for miserable outcome. Proportions of patients with good outcome were 94%, 83%, 70%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 3%, 9%, and 50% for 0 to 1, 2, 3, and 8 to 10 points, respectively. There was high correlation between predicted and observed probability of 3-month favorable and miserable outcome in the external validation cohort (Pearson correlation coefficient, .98 and .98, respectively, both P < .0001). The DRAGON score showed good performance to predict functional outcome after tissue-type plasminogen activator treatment in the Chinese population. This study demonstrated the accuracy and usability of the DRAGON score in the Chinese population in daily practice. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pre-hospital Delay as Determinant of Ischemic Stroke Outcome in an Italian Cohort of Patients Not Receiving Thrombolysis.

PubMed

Denti, Licia; Artoni, Andrea; Scoditti, Umberto; Gatti, Elisa; Bussolati, Chiara; Ceda, Gian Paolo

2016-06-01

Pre-hospital delay in acute stroke is critical to the administration of thrombolysis and affects patients' clinical outcome. In this study, the impact of pre-hospital delay on the outcome of ischemic stroke was investigated in an Italian cohort of patients who did not receive thrombolysis. Data from a cohort of 1847 patients, suffering from first-ever ischemic stroke and referred to an in-hospital clinical pathway were analyzed retrospectively. The relationship between pre-hospital delay and 1-month mortality was assessed with adjustment for demographics, premorbid disability, and stroke severity, which was graded according to the Scandinavian Stroke Scale, with higher scores indicating less severity. Five hundred and twelve patients (27.7%) arrived at hospital within 2 hours of symptom onset. A significant correlation was found between early arrival and a reduced risk of 1-month mortality (hazard ratio .65; 95% confidence interval .48-.89; P = .02). There was a significant interaction (P = .01) between pre-hospital delay and the neurological score on mortality in the multivariate model, and the survival advantage of early admission was significant only for patients with scores on the Scandinavian Stroke Scale less than 18 (hazard ratio .54; 95% confidence interval .34-.85; P = .008). Our study suggests that reducing pre-hospital delay can increase the probability of survival in patients with ischemic stroke, especially those who are most severely affected. Even if the patients cannot benefit from thrombolysis, survival rates can be increased provided that they are managed according to standardized care processes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.