FAK-heterozygous mice display enhanced tumour angiogenesis.
Kostourou, Vassiliki; Lechertier, Tanguy; Reynolds, Louise E; Lees, Delphine M; Baker, Marianne; Jones, Dylan T; Tavora, Bernardo; Ramjaun, Antoine R; Birdsey, Graeme M; Robinson, Stephen D; Parsons, Maddy; Randi, Anna M; Hart, Ian R; Hodivala-Dilke, Kairbaan
2013-01-01
Genetic ablation of endothelial focal adhesion kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularization. Here we show that reduced stromal FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumour growth in vivo. Our results highlight a potential novel role for FAK as a nonlinear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis.
FAK-heterozygous mice display enhanced tumour angiogenesis
Kostourou, Vassiliki; Lechertier, Tanguy; Reynolds, Louise E.; Lees, Delphine M.; Baker, Marianne; Jones, Dylan T.; Tavora, Bernardo; Ramjaun, Antoine R.; Birdsey, Graeme M.; Robinson, Stephen D.; Parsons, Maddy; Randi, Anna M.; Hart, Ian R; Hodivala-Dilke, Kairbaan
2013-01-01
Genetic ablation of endothelial Focal Adhesion Kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularisation. Here we show that reduced stromal-FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumor growth in vivo. Our results highlight a potential novel role for FAK as a non-linear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis. PMID:23799510
Inhibition of pressure-activated cancer cell adhesion by FAK-derived peptides
Zeng, Bixi; Devadoss, Dinesh; Wang, Shouye; Vomhof-DeKrey, Emilie E.; Kuhn, Leslie A.; Basson, Marc D.
2017-01-01
Forces within the surgical milieu or circulation activate cancer cell adhesion and potentiate metastasis through signaling requiring FAK-Akt1 interaction. Impeding FAK-Akt1 interaction might inhibit perioperative tumor dissemination, facilitating curative cancer surgery without global FAK or AKT inhibitor toxicity. Serial truncation and structurally designed mutants of FAK identified a seven amino acid, short helical structure within FAK that effectively competes with Akt1-FAK interaction. Adenoviral overexpression of this FAK-derived peptide inhibited pressure-induced FAK phosphorylation and AKT-FAK coimmunoprecipitation in human SW620 colon cancer cells briefly exposed to 15mmHg increased pressure, consistent with laparoscopic or post-surgical pressures. Adenoviral FAK-derived peptide expression prevented pressure-activation of SW620 adhesion not only to collagen-I-coated plates but also to murine surgical wounds. A scrambled peptide did not. Finally, we modeled operative shedding of tumor cells before irrigation and closure by transient cancer cell adhesion to murine surgical wounds before irrigation and closure. Thirty minute preincubation of SW620 cells at 15mmHg increased pressure impaired subsequent tumor free survival in mice exposed to cells expressing the scrambled peptide. The FAK-derived sequence prevented this. These results suggest that blocking FAK-Akt1 interaction may prevent perioperative tumor dissemination and that analogs or mimics of this 7 amino acid FAK-derived peptide could impair metastasis. PMID:29228673
FAK Regulates Intestinal Epithelial Cell Survival and Proliferation during Mucosal Wound Healing
Tilghman, Robert W.; Casanova, James E.; Bouton, Amy H.
2011-01-01
Background Following damage to the intestinal epithelium, restoration of epithelial barrier integrity is triggered by a robust proliferative response. In other tissues, focal adhesion kinase (FAK) regulates many of the cellular processes that are critical for epithelial homeostasis and restitution, including cell migration, proliferation and survival. However, few studies to date have determined how FAK contributes to mucosal wound healing in vivo. Methodology and Principal Findings To examine the role of FAK in intestinal epithelial homeostasis and during injury, we generated intestinal epithelium (IE)-specific conditional FAK knockout mice. Colitis was induced with dextran-sulfate-sodium (DSS) and intestinal tissues were analyzed by immunohistochemistry and immunoblotting. While intestinal development occurred normally in mice lacking FAK, FAK-deficient animals were profoundly susceptible to colitis. The loss of epithelial FAK resulted in elevated p53 expression and an increased sensitivity to apoptosis, coincident with a failure to upregulate epithelial cell proliferation. FAK has been reported to function as a mechanosensor, inducing cyclin D1 expression and promoting cell cycle progression under conditions in which tissue/matrix stiffness is increased. Collagen deposition, a hallmark of inflammatory injury resulting in increased tissue rigidity, was observed in control and FAK knockout mice during colitis. Despite this fibrotic response, the colonic epithelium in FAK-deficient mice exhibited significantly reduced cyclin D1 expression, suggesting that proliferation is uncoupled from fibrosis in the absence of FAK. In support of this hypothesis, proliferation of Caco-2 cells increased proportionally with matrix stiffness in vitro only under conditions of normal FAK expression; FAK depleted cells exhibited reduced proliferation concomitant with attenuated cyclin D1 expression. Conclusions In the colon, FAK functions as a regulator of epithelial cell survival and
Alexopoulou, Annika N; Lees, Delphine M; Bodrug, Natalia; Lechertier, Tanguy; Fernandez, Isabelle; D'Amico, Gabriela; Dukinfield, Matthew; Batista, Silvia; Tavora, Bernardo; Serrels, Bryan; Hodivala-Dilke, Kairbaan
2017-07-01
Focal adhesion kinase (FAK) inhibitors have been developed as potential anticancer agents and are undergoing clinical trials. In vitro activation of the FAK kinase domain triggers autophosphorylation of Y397, Src activation, and subsequent phosphorylation of other FAK tyrosine residues. However, how FAK Y397 mutations affect FAK kinase-dead (KD) phenotypes in tumour angiogenesis in vivo is unknown. We developed three Pdgfb-iCre ert -driven endothelial cell (EC)-specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT), FAK KD, and FAK double mutant (DM), i.e. KD with a putatively phosphomimetic Y397E mutation. These ECCre+;FAK WT / WT , ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice were injected subcutaneously with syngeneic B16F0 melanoma cells. Tumour growth and tumour blood vessel functions were unchanged between ECCre+;FAK WT / WT and ECCre-;FAK WT / WT control mice. In contrast, tumour growth and vessel density were decreased in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice, as compared with Cre - littermates. Despite no change in the percentage of perfused vessels or pericyte coverage in either genotype, tumour hypoxia was elevated in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice. Furthermore, although ECCre+;FAK KD / KD mice showed reduced blood vessel leakage, ECCre+;FAK DM / DM and ECCre-;FAK DM / DM mice showed no difference in leakage. Mechanistically, fibronectin-stimulated Y397 autophosphorylation was reduced in Cre+;FAK KD / KD ECs as compared with Cre+;FAK WT / WT cells, with no change in phosphorylation of the known Src targets FAK-Y577, FAK-Y861, FAK-Y925, paxillin-Y118, p130Cas-Y410. Cre+;FAK DM / DM ECs showed decreased Src target phosphorylation levels, suggesting that the Y397E substitution actually disrupted Src activation. Reduced VE-cadherin-pY658 levels in Cre+;FAK KD / KD ECs were rescued in Cre+FAK DM / DM ECs, corresponding with the rescue in vessel leakage in the ECCre+;FAK DM / DM mice. We show that EC
The FAK scaffold inhibitor C4 disrupts FAK-VEGFR-3 signaling and inhibits pancreatic cancer growth
Kurenova, Elena; Liao, Jianqun; He, Di-Hua; Hunt, Darrell; Yemma, Michael; Bshara, Wiam; Seshadri, Mukund; Cance, William G.
2013-01-01
Even with successful surgical resection and perioperative chemotherapy and radiation, pancreatic ductal adenocarcinoma (PDA) has a high incidence of recurrence. Tumor cell survival depends on activation of signaling pathways that suppress the apoptotic stimuli of invasion and metastasis. Focal adhesion kinase (FAK) is a critical signaling molecule that has been implicated in tumor cell survival, invasion and metastasis. We have previously shown that FAK and vascular endothelial growth factor receptor 3 (VEGFR-3) are overexpressed in cancer cells and physically interact to confer a significant survival advantage. We subsequently identified a novel small molecule inhibitor C4 that targeted the VEGFR-3-FAK site of interaction. In this study, we have shown that C4 disrupted the FAK-VEGFR-3 complexes in PDA cells. C4 treatment caused dose-dependent dephosphorylation and inactivation of the VEGFR-3 and FAK, reduction in cell viability and proliferation, cell cycle arrest and apoptosis in PDA cells. C4 increased the sensitivity of tumor cells to gemcitabine chemotherapy in vitro that lead to apoptosis at nanomolar concentrations of both drugs. C4 reduced tumor growth in vivoin subcutaneous and orthotopic murine models of PDA. The drug alone at low dose, decreased tumor growth; however, concomitant administration with low dose of gemcitabine had significant synergistic effect and led to 70% tumor reduction. Combination of C4 with gemcitabine had a prolonged cytostatic effect on tumor growth after treatment withdrawal. Finally, we report an anecdotal case of stage IV pancreatic cancer treated with gemcitabine in combination with C4 that showed a significant clinical response in primary tumor and complete clinical response in liver metastasis over an eight month period. Taken together, these results demonstrate that targeting the scaffolding function of FAK with a small-molecule FAK-VEGFR-3 inhibitor can be an effective therapeutic strategy against PDA. PMID:24142503
Marlowe, Timothy A; Lenzo, Felicia L; Figel, Sheila A; Grapes, Abigail T; Cance, William G
2016-12-01
Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTK High cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTK Low cells. Finally, HER2 +: cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2 + cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028-39. ©2016 AACR. ©2016 American Association for Cancer Research.
RELM-β promotes human pulmonary artery smooth muscle cell proliferation via FAK-stimulated surviving
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Chunlong, E-mail: lclmd@sina.com; Li, Xiaohui; Luo, Qiong
Resistin-like molecule-β (RELM-β), focal adhesion kinase (FAK), and survivin may be involved in the proliferation of cultured human pulmonary artery smooth muscle cells (HPAMSCs), which is involved in pulmonary hypertension. HPAMSCs were treated with human recombinant RELM-β (rhRELM-β). siRNAs against FAK and survivin were transfected into cultured HPASMCs. Expression of FAK and survivin were examined by RT-PCR and western blot. Immunofluorescence was used to localize FAK. Flow cytometry was used to examine cell cycle distribution and cell death. Compared to the control group, all rhRELM-β-treated groups demonstrated significant increases in the expression of FAK and survivin (P<0.05). rhRELM-β significantly increasedmore » the proportion of HPASMCs in the S phase and decreased the proportion in G0/G1. FAK siRNA down-regulated survivin expression while survivin siRNA did not affect FAK expression. FAK siRNA effectively inhibited FAK and survivin expression in RELM-β-treated HPASMCs and partially suppressed cell proliferation. RELM-β promoted HPASMC proliferation and upregulated FAK and survivin expression. In conclusion, results suggested that FAK is upstream of survivin in the signaling pathway mediating cell proliferation. FAK seems to be important in RELM-β-induced HPASMC proliferation, partially by upregulating survivin expression. - Highlights: • rhRELM-β increased the expression of FAK and survivin. • rhRELM-β increased the proportion of HPASMCs in the S phase. • FAK is upstream of survivin in the signaling pathway mediating cell proliferation. • FAK is important in RELM-β-induced HPASMC proliferation, partly via survivin.« less
Marlowe, Timothy A.; Lenzo, Felicia L.; Figel, Sheila A.; Grapes, Abigail T.; Cance, William G.
2016-01-01
Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms which drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTKs) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK’s critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. Additionally, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: 1) the rapid phosphorylation and activation of RTK signaling pathways in RTKHigh cells and 2) the long-term acquisition of RTKs novel to the parental cell line in RTKLow cells. Finally, HER2+ cancer cells displayed resistance to FAK-kinase inhibition in 3D–growth assays using a HER2 isogenic system and HER2+ cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. PMID:27638858
FAK Inhibition Decreases Hepatoblastoma Survival Both In Vitro and In Vivo12
Gillory, Lauren A; Stewart, Jerry E; Megison, Michael L; Nabers, Hugh C; Mroczek-Musulman, Elizabeth; Beierle, Elizabeth A
2013-01-01
Hepatoblastoma is the most frequently diagnosed liver tumor of childhood, and children with advanced, metastatic or relapsed disease have a disease-free survival rate under 50%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumor development and progression. FAK has been found in other pediatric solid tumors and in adult hepatocellular carcinoma, leading us to hypothesize that FAK would be present in hepatoblastoma and would impact its cellular survival. In the current study, we showed that FAK was present and phosphorylated in human hepatoblastoma tumor specimens. We also examined the effects of FAK inhibition upon hepatoblastoma cells using a number of parallel approaches to block FAK including RNAi and small molecule FAK inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and migration and increased apoptosis. Further, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse xenograft model of hepatoblastoma. The findings from this study will help to further our understanding of the regulation of hepatoblastoma tumorigenesis and may provide desperately needed novel therapeutic strategies and targets for aggressive, recurrent, or metastatic hepatoblastomas. PMID:23544173
Netrin-1 attracts axons through FAK-dependent mechanotransduction.
Moore, Simon W; Zhang, Xian; Lynch, Christopher D; Sheetz, Michael P
2012-08-22
The mechanism by which extracellular cues influence intracellular biochemical cascades that guide axons is important, yet poorly understood. Because of the mechanical nature of axon extension, we explored whether the physical interactions of growth cones with their guidance cues might be involved. In the context of mouse spinal commissural neuron axon attraction to netrin-1, we found that mechanical attachment of netrin-1 to the substrate was required for axon outgrowth, growth cone expansion, axon attraction and phosphorylation of focal adhesion kinase (FAK) and Crk-associated substrate (CAS). Myosin II activity was necessary for traction forces >30 pN on netrin-1. Interestingly, while these myosin II-dependent forces on netrin-1 substrates or beads were needed to increase the kinase activity and phosphorylation of FAK, they were not necessary for netrin-1 to increase CAS phosphorylation. When FAK kinase activity was inhibited, the growth cone's ability to recruit additional adhesions and to generate forces >60 pN on netrin-1 was disrupted. Together, these findings demonstrate an important role for mechanotransduction during chemoattraction to netrin-1 and that mechanical activation of FAK reinforces interactions with netrin-1 allowing greater forces to be exerted.
Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie
2017-08-01
To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.
Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo
2017-07-12
Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but
FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal.
Haemmerle, Monika; Bottsford-Miller, Justin; Pradeep, Sunila; Taylor, Morgan L; Choi, Hyun-Jin; Hansen, Jean M; Dalton, Heather J; Stone, Rebecca L; Cho, Min Soon; Nick, Alpa M; Nagaraja, Archana S; Gutschner, Tony; Gharpure, Kshipra M; Mangala, Lingegowda S; Rupaimoole, Rajesha; Han, Hee Dong; Zand, Behrouz; Armaiz-Pena, Guillermo N; Wu, Sherry Y; Pecot, Chad V; Burns, Alan R; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K
2016-05-02
Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management.
FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal
Haemmerle, Monika; Bottsford-Miller, Justin; Pradeep, Sunila; Taylor, Morgan L.; Hansen, Jean M.; Dalton, Heather J.; Stone, Rebecca L.; Cho, Min Soon; Nick, Alpa M.; Nagaraja, Archana S.; Gutschner, Tony; Gharpure, Kshipra M.; Mangala, Lingegowda S.; Han, Hee Dong; Zand, Behrouz; Armaiz-Pena, Guillermo N.; Wu, Sherry Y.; Pecot, Chad V.; Burns, Alan R.; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K.
2016-01-01
Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management. PMID:27064283
Zhao, Xiaofeng; Peng, Xu; Sun, Shaogang; Park, Ann Y J; Guan, Jun-Lin
2010-06-14
Focal adhesion kinase (FAK) is essential for vascular development as endothelial cell (EC)-specific knockout of FAK (conditional FAK knockout [CFKO] mice) leads to embryonic lethality. In this study, we report the differential kinase-independent and -dependent functions of FAK in vascular development by creating and analyzing an EC-specific FAK kinase-defective (KD) mutant knockin (conditional FAK knockin [CFKI]) mouse model. CFKI embryos showed apparently normal development through embryonic day (E) 13.5, whereas the majority of CFKO embryos died at the same stage. Expression of KD FAK reversed increased EC apoptosis observed with FAK deletion in embryos and in vitro through suppression of up-regulated p21. However, vessel dilation and defective angiogenesis of CFKO embryos were not rescued in CFKI embryos. ECs without FAK or expressing KD FAK showed increased permeability, abnormal distribution of vascular endothelial cadherin (VE-cadherin), and reduced VE-cadherin Y658 phosphorylation. Together, our data suggest that kinase-independent functions of FAK can support EC survival in vascular development through E13.5 but are insufficient for maintaining EC function to allow for completion of embryogenesis.
Yanoshita, Makoto; Hirose, Naoto; Okamoto, Yuki; Sumi, Chikako; Takano, Mami; Nishiyama, Sayuri; Asakawa-Tanne, Yuki; Horie, Kayo; Onishi, Azusa; Yamauchi, Yuka; Mitsuyoshi, Tomomi; Kunimatsu, Ryo; Tanimoto, Kotaro
2018-05-08
Excessive mechanical stimulation is considered an important factor in the destruction of chondrocytes. Focal adhesion kinase (FAK) is non-receptor tyrosine kinase related to a number of different signaling proteins. Little is known about the function of FAK in chondrocytes under mechanical stimulation. In the present study, we investigated the function of FAK in mechanical signal transduction and the mechanism through which cyclic tensile strain (CTS) induces expression of inflammation-related factors. Mouse ATDC5 chondrogenic cells were subjected to CTS of 0.5 Hz to 10% cell elongation with an FAK inhibitor. The expression of genes encoding COX-2, IL-1β, and TNF-α was examined using real-time RT-PCR after CTS application with FAK inhibitor. Phosphorylation of p-38, ERK, and JNK was analyzed by Western blotting. Differences in COX-2 expression following pretreatment with FAK, p-38, ERK, and JNK inhibitors were compared by Western blotting. We found that CTS increased the expression of genes encoding COX-2, IL-1β, and TNF-α and activated the phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with an FAK inhibitor for 2 h reduced the expression of genes encoding COX-2, IL-1β, and TNF-α induced by CTS-associated inflammation and decreased phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with FAK, p-38, ERK, and JNK inhibitors markedly suppressed COX-2 and IL-1β protein expression. In conclusion, FAK appears to regulate inflammation in chondrocytes under CTS via MAPK pathways.
Zhang, Yingchi; Yan, Jiyuan; Xu, Haoran; Yang, Yong; Li, Wenkai; Wu, Hua; Liu, Chaoxu
2018-05-21
The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs. With the use of Helmholtz coils and an EMF stimulator, 7.5, 15, 30, 50, and 70 Hz/1 mT EMF was generated. Additionally, we employed the L-type calcium channel blocker verapamil and the focal adhesion kinase (FAK) inhibitor PF-573228 to investigate the role of intracellular calcium content, cell adhesion proteins, and the Rho GTPase protein family (RhoA, Rac1, and Cdc42) in EMF-mediated MSC migration. Cell adhesion proteins (FAK, talin, and vinculin) were detected by Western blot analysis. The Rho GTPase protein family activities were assessed by G-LISA, and F-actin levels, which reflect actin cytoskeletal organization, were detected using immunofluorescence. All the 7.5, 15, 30, 50, and 70 Hz/1 mT EMF promoted MSC migration. EMF increased MSC migration in an intracellular calcium-dependent manner. Notably, EMF-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased talin and vinculin expression. Moreover, RhoA, Rac1, and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. EMF promoted MSC migration by increasing intracellular calcium and activating the FAK/Rho GTPase signaling pathways. This study provides insights into the mechanisms of MSC migration and will enable the rational design of targeted therapies to improve MSC engraftment.
Effect of Acupotomy on FAK-PI3K Signaling Pathways in KOA Rabbit Articular Cartilages
Xie, Zhan-guo; Guo, Yan; Yu, Jia-Ni; Lu, Juan; Zhang, Wei; Wang, Li-Juan; Xu, Jing; Zhao, Rui-Li; Zhou, Shuai
2017-01-01
Objective By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. Method 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. Results Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). Conclusion Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism. PMID:29234400
Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad
2017-01-01
Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding.
Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad
2017-01-01
Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding. PMID:29081606
Naringin suppresses the development of glioblastoma by inhibiting FAK activity.
Li, Jinjiang; Dong, Yushu; Hao, Guangzhi; Wang, Bao; Wang, Julei; Liang, Yong; Liu, Yangyang; Zhen, Endi; Feng, Dayun; Liang, Guobiao
2017-01-01
As the most common and lethal primary malignant brain cancer, glioblastoma is hard to timely diagnose and sensitive therapeutic monitoring. It is essential to develop new and effective drugs for glioblastoma multiform. Naringin belongs to citrus flavonoids and was found to display strong anti-inflammatory, antioxidant and antitumor activities. In this report, we found that naringin can specifically inhibit the kinase activity of FAK and suppress the FAK p-Try397 and its downstream pathway in glioblastoma cells. Our study showed out that naringin can inhibit cell proliferation by inhibiting FAK/cyclin D1 pathway, promote cell apoptosis through influencing FAK/bads pathway, at the same time, it can also inhibit cell invasion and metastasis by inhibiting the FAK/mmps pathway. All these showed that naringin exerts the anti-tumor effects in U87 MG by inhibiting the kinase activity of FAK.
Cortactin as a Target for FAK in the Regulation of Focal Adhesion Dynamics
Ghassemian, Majid; Schlaepfer, David D.
2012-01-01
Background Efficient cell movement requires the dynamic regulation of focal adhesion (FA) formation and turnover. FAs are integrin-associated sites of cell attachment and establish linkages to the cellular actin cytoskeleton. Cells without focal adhesion kinase (FAK), an integrin-activated tyrosine kinase, exhibit defects in FA turnover and cell motility. Cortactin is an actin binding adaptor protein that can influence FA dynamics. FAK and cortactin interact, but the cellular role of this complex remains unclear. Principal Findings Using FAK-null fibroblasts stably reconstituted with green fluorescent protein (GFP) tagged FAK constructs, we find that FAK activity and FAK C-terminal proline-rich region 2 (PRR2) and PRR3 are required for FA turnover and cell motility. Cortactin binds directly to FAK PRR2 and PRR3 sites via its SH3 domain and cortactin expression is important in promoting FA turnover and GFP-FAK release from FAs. FAK-cortactin binding is negatively-regulated by FAK activity and associated with cortactin tyrosine phosphorylation. FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility. However, phospho-mimetic cortactin mutated to glutamic acid (3YE) did not affect FA dynamics and did not rescue FA turnover defects in cells with inhibited FAK activity or with PRR2-mutated FAK that does not bind cortactin. Conclusions Our results support a model whereby FAK-mediated FA remodeling may occur through the formation of a FAK-cortactin signaling complex. This involves a cycle of cortactin binding to FAK, cortactin tyrosine phosphorylation, and subsequent cortactin-FAK dissociation accompanied by FA turnover and cell movement. PMID:22952866
The Role of FAK in the Secretion of MMP9 after CD147 Stimulation in Macrophages.
Yu, Chen; Lixia, Yang; Ruiwei, Guo; Yankun, Shi; Jinshan, Ye
2018-03-30
To investigate whether focal adhesion kinase (FAK) can participate in the secretion of matrix metalloproteinase 9 (MMP9) after CD147 stimulation in THP-1 induced macrophages; thus, to explore the potential treatment perspectives for acute coronary syndrome (ACS).Phorbol-12-myristate-13-acetate (PMA) was used to induce THP-1 cells to differentiate into macrophages. To confirm the peak mRNA and protein expression of FAK and MMP9 after the stimulation of CD147, the macrophages were divided into 5 groups (0, 3, 6, 9, and 12 hours), with 0 hours group as control group. To investigate the role of FAK in the secretion of MMP9, with stimulation of CD147 for 9 hours, FAK inhibitor 14 was used to inhibit FAK Y397 phosphorylation. The mRNA and protein expressions were quantified by qRT-PCR and western blotting, respectively. (1) Relative mRNA expression of FAK and MMP9 were both significantly up-regulated (all P < 0.05) after stimulation of CD147, FAK peaked at 9 hours (3.908 ± 0.106 versus 1, P < 0.05), whereas MMP9 peaked at 6 hours (2.522 ± 0.062 versus 1, P < 0.05). (2) Relative protein expression of FAK, pFAK, and MMP9 were all significantly increased after CD147 stimulation (all P < 0.05), FAK (1.930 ± 0.024 versus 1, P < 0.05) and pFAK (1.737 ± 0.021 versus 1, P < 0.05) peaked at 9 hours, whereas MMP9 peaked at 6 hours (1.527 ± 0.033 versus 1, P < 0.05). (3) CD147 up-regulates FAK, pFAK, and MMP9 mRNA and protein expressions in a dose-dependent manner. (4) FAK inhibitor 14 significantly reduced the relative protein expression level of pFAK (0.077 ± 0.012 versus 1, P < 0.05) and MMP9 (0.133 ± 0.012) at 9 hours after CD147 stimulation.The results demonstrated that FAK Y397 phosphorylation was involved in the secretion of MMP9 after CD147 stimulation in macrophages and may play a role in the regulation of ACS.
Requirement of PEA3 for Transcriptional Activation of FAK Gene in Tumor Metastasis
Li, Shufeng; Huang, Xiaofeng; Zhang, Dapeng; Huang, Qilai; Pei, Guoshun; Wang, Lixiang; Jiang, Wenhui; Hu, Qingang; Tan, Renxiang; Hua, Zi-Chun
2013-01-01
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critically involved in cancer metastasis. We found an elevation of FAK expression in highly metastatic melanoma B16F10 cells compared with its less metastatic partner B16F1 cells. Down-regulation of the FAK expression by either small interfering RNA or dominant negative FAK (FAK Related Non-Kinase, FRNK) inhibited the B16F10 cell migration in vitro and invasiveness in vivo. The mechanism by which FAK activity is up-regulated in highly metastatic cells remains unclear. In this study, we reported for the first time that one of the Est family proteins, PEA3, is able to transactivate FAK expression through binding to the promoter region of FAK. We identified a PEA3-binding site between nucleotides −170 and +43 in the FAK promoter that was critical for the responsiveness to PEA3. A stronger affinity of PEA3 to this region contributed to the elevation of FAK expression in B16F10 cells. Both in vitro and in vivo knockdown of PEA3 gene successfully mimicked the cell migration and invasiveness as that induced by FAK down-regulation. The activation of the well-known upstream of PEA3, such as epidermal growth factor, JNK, and ERK can also induce FAK expression. Furthermore, in the metastatic human clinic tumor specimens from the patients with human primary oral squamous cell carcinoma, we observed a strong positive correlation among PEA3, FAK, and carcinoma metastasis. Taking together, we hypothesized that PEA3 might play an essential role in the activation of the FAK gene during tumor metastasis. PMID:24260201
Differential Expression of FAK and Pyk2 in Metastatic and Non-metastatic EL4 Lymphoma Cell Lines
Zhang, Zhihong; Knoepp, Stewart M.; Ku, Hsun; Sansbury, Heather M.; Xie, Yuhuan; Chahal, Manpreet S.; Tomlinson, Stephen; Meier, Kathryn E.
2011-01-01
The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells. PMID:21533871
Differential expression of FAK and Pyk2 in metastatic and non-metastatic EL4 lymphoma cell lines.
Zhang, Zhihong; Knoepp, Stewart M; Ku, Hsun; Sansbury, Heather M; Xie, Yuhuan; Chahal, Manpreet S; Tomlinson, Stephen; Meier, Kathryn E
2011-08-01
The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells.
Megison, Michael L.; Gillory, Lauren A.; Stewart, Jerry E.; Nabers, Hugh C.; Mrozcek-Musulman, Elizabeth; Beierle, Elizabeth A.
2014-01-01
Despite the tremendous advances in the treatment of childhood kidney tumors, there remain subsets of pediatric renal tumors that continue to pose a therapeutic challenge, mainly malignant rhabdoid kidney tumors and non-osseous renal Ewing sarcoma. Children with advanced, metastatic or relapsed disease have a disease-free survival rate under 30%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumor development and progression. FAK has been found in other pediatric solid tumors and in adult renal cellular carcinoma, leading us to hypothesize that FAK would be present in pediatric kidney tumors and would impact their cellular survival. In the current study, we showed that FAK was present and phosphorylated in pediatric kidney tumor specimens. We also examined the effects of FAK inhibition upon G401 and SK-NEP-1 cell lines utilizing a number of parallel approaches to block FAK including RNAi and small molecule FAK inhibitors. FAK inhibition resulted in decreased cellular survival, invasion and migration, and increased apoptosis. Further, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse SK-NEP-1 xenograft model. The findings from this study will help to further our understanding of the regulation of tumorigenesis in rare pediatric renal tumors, and may provide desperately needed novel therapeutic strategies and targets for these rare, but difficult to treat, malignancies. PMID:24464916
Skinner, Heath D; Giri, Uma; Yang, Liang; Woo, Sang Hyeok; Story, Michael D; Pickering, Curtis R; Byers, Lauren A; Williams, Michelle D; El-Naggar, Adel; Wang, Jing; Diao, Lixia; Shen, Li; Fan, You Hong; Molkentine, David P; Beadle, Beth M; Meyn, Raymond E; Myers, Jeffrey N; Heymach, John V
2016-09-15
Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date, human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC. We performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC. Increased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2-M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS; P = 0.012 and 0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P = 0.03). Moreover, both PTK2/FAK mRNA (P = 0.021) and copy number (P = 0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas. Proteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. Clin Cancer Res; 22(18); 4643-50. ©2016 AACR. ©2016 American Association for Cancer Research.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Bingyu; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Mao, Xinjian
Tendon injuries are common in sports and are frequent reasons for orthopedic consultations. The management of damaged tendons is one of the most challenging problems in orthopedics. Mechano-growth factor (MGF), a recently discovered growth repair factor, plays positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. We used a scratch wound assay in this study to demonstrate that MGF-C25E (a synthetic mechano-growth factor E peptide) promotes the migration of rat tenocytes and that this promotionmore » is accompanied by an elevation in the expression of the following signaling molecules: focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2). Inhibitors of the FAK and ERK1/2 pathways inhibited the MGF-C25E-induced tenocyte migration, indicating that MGF-C25E promotes tenocyte migration through the FAK-ERK1/2 signaling pathway. The analysis of the mechanical properties showed that the Young's modulus of tenocytes was decreased through treatment of MGF-C25E, and an obvious formation of pseudopodia and F-actin was observed in MGF-C25E-treated tenocytes. The inhibition of the FAK or ERK1/2 signals restored the decrease in Young's modulus and inhibited the formation of pseudopodia and F-actin. Overall, our study demonstrated that MGF-C25E promotes rat tenocyte migration by lessening cell stiffness and increasing pseudopodia formation via the FAK-ERK1/2 signaling pathway. - Highlights: • Mechano-growth factor E peptide (MGF-C25E) promotes migration of rat tenocytes. • MGF-C25E activates the FAK-ERK1/2 pathway in rat tenocytes. • MGF-C25E induces the actin remodeling and the formation of pseudopodia, and decreases the stiffness in rat tenocytes. • MGF-C25E promotes tenocyte migration via altering stiffness and forming pseudopodia by the activation of the
Focal adhesion kinase (FAK) regulates polymerase activity of multiple influenza A virus subtypes.
Elbahesh, Husni; Bergmann, Silke; Russell, Charles J
2016-12-01
Influenza A viruses (IAVs) cause numerous pandemics and yearly epidemics resulting in ~500,000 annual deaths globally. IAV modulates cellular signaling pathways at every step of the infection cycle. Focal adhesion kinase (FAK) has been shown to play a critical role in endosomal trafficking of influenza A viruses, yet it is unclear how FAK kinase activity regulates IAV replication. Using mini-genomes derived from H1N1, H5N1 and H7N9 viruses, we dissected RNA replication by IAVs independent of viral entry or release. Our results show FAK activity promotes efficient IAV polymerase activity and inhibiting FAK activity with a chemical inhibitor or a kinase-dead mutant significantly reduces IAV polymerase activity. Using co-immunoprecipitations and proximity ligation assays, we observed interactions between FAK and the viral nucleoprotein, supporting a direct role of FAK in IAV replication. Altogether, the data indicates that FAK kinase activity is important in promoting IAV replication by regulating its polymerase activity. Copyright © 2016 Elsevier Inc. All rights reserved.
Yang, Li-yun; He, Chang-yu; Chen, Xue-hua; Su, Li-ping; Liu, Bing-ya; Zhang, Hao
2016-01-01
Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. PMID:27356739
Guo, Shuhong; Nighot, Meghali; Al-Sadi, Rana; Alhmoud, Tarik; Nighot, Prashant; Ma, Thomas Y.
2015-01-01
Gut-derived bacterial lipopolysaccharides (LPS) play an essential role in inducing intestinal and systemic inflammatory responses and have been implicated as a pathogenic factor of necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). The defective intestinal tight junction (TJ) barrier has been shown to be an important factor contributing to the development of intestinal inflammation. LPS, at physiological concentrations, cause an increase in intestinal tight junction permeability (TJP) via a TLR-4 dependent process; however the intracellular mechanisms that mediate LPS regulation of intestinal TJP remain unclear. The aim of this study was to investigate the adaptor proteins and the signaling interactions that mediate LPS modulation of intestinal TJ barrier using an in-vitro and in-vivo model system. LPS caused a TLR-4 dependent activation of membrane-associated adaptor protein FAK in Caco-2 monolayers. LPS caused an activation of both MyD88-dependent and –independent pathways. SiRNA silencing of MyD88 prevented LPS-induced increase in TJP. LPS caused a MyD88-dependent activation of IRAK4. TLR-4, FAK and MyD88 were co-localized. SiRNA silencing of TLR-4 inhibited TLR-4 associated FAK activation; and FAK knockdown prevented MyD88 activation. In-vivo studies also confirmed that LPS-induced increase in mouse intestinal permeability was associated with FAK and MyD88 activation; knockdown of intestinal epithelial FAK prevented LPS-induced increase in intestinal permeability. Additionally, high dose LPS-induced intestinal inflammation was also dependent on TLR-4/FAK/MyD88 signal-transduction axis. Our data show for the first time that LPS-induced increase in intestinal TJP and intestinal inflammation was regulated by TLR-4 dependent activation of FAK-MyD88-IRAK4 signaling pathway. PMID:26466961
Amplification and oscillations in the FAK/Src kinase system during integrin signaling.
Caron-Lormier, G; Berry, H
2005-01-21
Integrin signaling is a major pathway of cell adhesion to extracellular matrices that regulates many physiological cell behaviors such as cell proliferation, migration or differentiation and is implied in pathologies such as tumor invasion. In this paper, we focused on the molecular system formed by the two kinases FAK (focal adhesion kinase) and Src, which undergo auto- and co-activation during early steps of integrin signaling. The system is modelled using classical kinetic equations and yields a set of three nonlinear ordinary differential equations describing the dynamics of the different phosphorylation forms of FAK. Analytical and numerical analysis of these equations show that this system may in certain cases amplify incoming signals from the integrins. A quantitative condition is obtained, which indicates that the total FAK charge in the system acts as a critical mass that must be exceeded for amplification to be effective. Furthermore, we show that when FAK activity is lower than Src activity, spontaneous oscillations of FAK phosphorylation forms may appear. The oscillatory behavior is studied using bifurcation and stability diagrams. We finally discuss the significance of this behavior with respect to recent experimental results evidencing FAK dynamics.
NASA Astrophysics Data System (ADS)
Heuslein, Joshua L.; Murrell, Kelsey P.; Leiphart, Ryan J.; Llewellyn, Ryan A.; Meisner, Joshua K.; Price, Richard J.
2016-05-01
Arteriogenesis, or the lumenal expansion of pre-existing arterioles in the presence of an upstream occlusion, is a fundamental vascular growth response. Though alterations in shear stress stimulate arteriogenesis, the migration of monocytes into the perivascular space surrounding collateral arteries and their differentiation into macrophages is critical for this vascular growth response to occur. Focal adhesion kinase’s (FAK) role in regulating cell migration has recently been expanded to primary macrophages. We therefore investigated the effect of the myeloid-specific conditional deletion of FAK on vascular remodeling in the mouse femoral arterial ligation (FAL) model. Using laser Doppler perfusion imaging, whole mount imaging of vascular casted gracilis muscles, and immunostaining for CD31 in gastrocnemius muscles cross-sections, we found that there were no statistical differences in perfusion recovery, arteriogenesis, or angiogenesis 28 days after FAL. We therefore sought to determine FAK expression in different myeloid cell populations. We found that FAK is expressed at equally low levels in Ly6Chi and Ly6Clo blood monocytes, however expression is increased over 2-fold in bone marrow derived macrophages. Ultimately, these results suggest that FAK is not required for monocyte migration to the perivascular space and that vascular remodeling following arterial occlusion occurs independently of myeloid specific FAK.
Golubovskaya, Vita; Palma, Nadia L.; Zheng, Min; Ho, Baotran; Magis, Andrew; Ostrov, David; Cance, William G.
2013-01-01
Focal Adhesion Kinase (FAK) is overexpressed in many types of tumors and plays an important role in survival. We developed a novel approach, targeting FAK-protein interactions by computer modeling and screening of NCI small molecule drug database. In this report we targeted FAK and Mdm-2 protein interaction to decrease tumor growth. By macromolecular modeling we found a model of FAK and Mdm-2 interaction and performed screening of >200,000 small molecule compounds from NCI database with drug-like characteristics, targeting the FAK-Mdm-2 interaction. We identified 5′-O-Tritylthymidine, called M13 compound that significantly decreased viability in different cancer cells. M13 was docked into the pocket of FAK and Mdm-2 interaction and was directly bound to the FAK-N terminal domain by ForteBio Octet assay. In addition, M13 compound affected FAK and Mdm-2 levels and decreased complex of FAK and Mdm-2 proteins in breast and colon cancer cells. M13 re-activated p53 activity inhibited by FAK with Mdm-2 promoter. M13 decreased viability, clonogenicity, increased detachment and apoptosis in a dose-dependent manner in BT474 breast and in HCT116 colon cancer cells in vitro. M13 decreased FAK, activated p53 and caspase-8 in both cell lines. In addition, M13 decreased breast and colon tumor growth in vivo. M13 activated p53 and decreased FAK in tumor samples consistent with decreased tumor growth. The data demonstrate a novel approach for targeting FAK and Mdm-2 protein interaction, provide a model of FAK and Mdm-2 interaction, identify M13 compound targeting this interaction and decreasing tumor growth that is critical for future targeted therapeutics. PMID:22292771
Jung, Oisun; Choi, Suyong; Jang, Sun-Bok; Lee, Sin-Ae; Lim, Ssang-Taek; Choi, Yoon-Ju; Kim, Hye-Jin; Kim, Do-Hee; Kwak, Tae Kyoung; Kim, Hyeonjung; Kang, Minkyung; Lee, Mi-Sook; Park, Sook Young; Ryu, Jihye; Jeong, Doyoung; Cheong, Hae-Kap; Kim, Hyun Jeong; Park, Ki Hun; Lee, Bong-Jin; Schlaepfer, David D.; Lee, Jung Weon
2012-01-01
Summary Transmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesion-dependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer. PMID:23077174
Grove, Matthew
2014-01-01
Without Focal Adhesion Kinase (FAK), developing murine Schwann cells (SCs) proliferate poorly, sort axons inefficiently, and cannot myelinate peripheral nerves. Here we show that FAK is required for the development of SCs when their basal lamina (BL) is fragmentary, but not when it is mature in vivo. Mutant SCs fail to spread on fragmentary BL during development in vivo, and this is phenocopied by SCs lacking functional FAK on low laminin (LN) in vitro. Furthermore, SCs without functional FAK initiate differentiation prematurely, both in vivo and in vitro. In contrast to their behavior on high levels of LN, SCs lacking functional FAK grown on low LN display reduced spreading, proliferation, and indicators of contractility (i.e., stress fibers, arcs, and focal adhesions) and are primed to differentiate. Growth of SCs lacking functional FAK on increasing LN concentrations in vitro revealed that differentiation is not regulated by G1 arrest but rather by cell spreading and the level of contractile actomyosin. The importance of FAK as a critical regulator of the specific response of developing SCs to fragmentary BL was supported by the ability of adult FAK mutant SCs to remyelinate demyelinated adult nerves on mature BL in vivo. We conclude that FAK promotes the spreading and actomyosin contractility of immature SCs on fragmentary BL, thus maintaining their proliferation, and preventing differentiation until they reach high density, thereby promoting radial sorting. Hence, FAK has a critical role in the response of SCs to limiting BL by promoting proliferation and preventing premature SC differentiation. PMID:25274820
Blocking FAK Signaling in the Tumor or Stroma and Effects on Metastasis
2010-04-01
5% sucrose controls (Fig. 2E and F ). In addition to inhibiting ascites-associated ID8 spheroid growth, PND-1186-treated mice showed significantly...as determined by anti-FaK followed by phospho-specific anti-FaK pY397 immu- noblotting. ( F ) Ratio of pY397 phospho- rylated FaK to total FaK levels...FAK pY397 by 0.5 mg/ml PND-1186 administration compared to 5% sucrose controls (Fig. 8E and F ). In addition to inhibiting ascites-associated ID8
Bianchi, Mariarita; De Lucchini, Stefania; Marin, Oriano; Turner, David L; Hanks, Steven K; Villa-Moruzzi, Emma
2005-10-15
In addition to tyrosine sites, FAK (focal adhesion kinase) is phosphorylated on multiple serine residues. In the present study, the regulation of two of these sites, Ser-722 (S1) and Ser-911 (S4), was investigated. Phosphorylation of S1 (but not S4) decreased in resuspended cells, and recovered during spreading on fibronectin, indicating adhesion-dependent regulation. GSK3 (glycogen synthase kinase 3) inhibitors decreased S1 phosphorylation, and siRNA (short interfering RNA) silencing indicated further the involvement of GSK3beta. Furthermore, GSK3beta was found to become activated during cell spreading on fibronectin, and to physically associate with FAK. S1 phosphorylation was observed to decrease in wounded cell monolayers, while GSK3beta underwent inactivation and later was observed to increase to the original level within 24 h. Direct phosphorylation of S1, requiring pre-phosphorylation of Ser-726 in the +4 position, was demonstrated using purified GSK3 and a synthetic peptide containing FAK residues 714-730. An inhibitory role for S1 phosphorylation in FAK signalling was indicated by findings that both alanine substitution for S1 and dephosphorylation of S1 by PP1 (serine/threonine protein phosphatase type-1) resulted in an increase in FAK kinase activity; likewise, this role was also shown by cell treatment with the GSK3 inhibitor LiCl. The inhibitory role was confirmed by the finding that cells expressing FAK with alanine substitution for S1 displayed improved cell spreading and faster migration in wound-healing and trans-well assays. Finally, the finding that S1 phosphorylation increased in cells treated with the PP1 inhibitor okadaic acid indicated targeting of this site by PP1. These results indicate an additional mechanism for regulation of FAK activity during cell spreading and migration, involving Ser-722 phosphorylation modulated through the competing actions of GSK3beta and PP1.
Kerstein, Patrick C.; Patel, Kevin M.
2017-01-01
Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca2+) is an essential signal for axon guidance that mediates opposing effects on growth cone motility. The diverse effects of Ca2+ arise from the precise localization of Ca2+ signals into microdomains containing specific Ca2+ effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca2+ signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain. However, how calpain regulates growth cone motility remains unclear. Here, we identify the adhesion proteins talin and focal adhesion kinase (FAK) as proteolytic targets of calpain in Xenopus laevis spinal cord neurons both in vivo and in vitro. Inhibition of calpain increases the localization of endogenous adhesion signaling to growth cone filopodia. Using live cell microscopy and specific calpain-resistant point-mutants of talin (L432G) and FAK (V744G), we find that calpain inhibits paxillin-based adhesion assembly through cleavage of talin and FAK, and adhesion disassembly through cleavage of FAK. Blocking calpain cleavage of talin and FAK inhibits repulsive turning from focal uncaging of Ca2+ within filopodia. In addition, blocking calpain cleavage of talin and FAK in vivo promotes Rohon–Beard peripheral axon extension into the skin. These data demonstrate that filopodial Ca2+ signals regulate axon outgrowth and guidance through calpain regulation of adhesion dynamics through specific cleavage of talin and FAK. SIGNIFICANCE STATEMENT The proper formation of neuronal networks requires accurate guidance of axons and dendrites during development by motile structures known as growth cones. Understanding the intracellular signaling mechanisms that govern growth cone motility will clarify how the nervous system develops and regenerates, and may
Taylor, Joan M.; Mack, Christopher P.; Nolan, Kate; Regan, Christopher P.; Owens, Gary K.; Parsons, J. Thomas
2001-01-01
Extracellular matrix signaling via integrin receptors is important for smooth muscle cell (SMC) differentiation during vasculogenesis and for phenotypic modulation of SMCs during atherosclerosis. We previously reported that the noncatalytic carboxyl-terminal protein binding domain of focal adhesion kinase (FAK) is expressed as a separate protein termed FAK-related nonkinase (FRNK) and that ectopic expression of FRNK can attenuate FAK activity and integrin-dependent signaling (A. Richardson and J. T. Parsons, Nature 380:538–540, 1996). Herein we report that in contrast to FAK, which is expressed ubiquitously, FRNK is expressed selectively in SMCs, with particularly high levels observed in conduit blood vessels. FRNK expression was low during embryonic development, was significantly upregulated in the postnatal period, and returned to low but detectable levels in adult tissues. FRNK expression was also dramatically upregulated following balloon-induced carotid artery injury. In cultured rat aortic smooth muscle cells, overexpression of FRNK attenuated platelet-derived growth factor (PDGF)-BB-induced migration and also dramatically inhibited [3H]thymidine incorporation upon stimulation with PDGF-BB or 10% serum. These effects were concomitant with a reduction in SMC proliferation. Taken together, these data indicate that FRNK acts as an endogenous inhibitor of FAK signaling in SMCs. Furthermore, increased FRNK expression following vascular injury or during development may alter the SMC phenotype by negatively regulating proliferative and migratory signals. PMID:11238893
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong
2012-07-13
Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all ofmore » which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice
Usage of heparan sulfate, integrins, and FAK in HPV16 infection
Abban, Cynthia Y.; Meneses, Patricio I.
2010-01-01
Human Papillomavirus Type 16 (HPV16) is the major causative agent of cervical cancer. Studies regarding the early binding and signaling molecules that play a significant role in infection are still lacking. The current study analyses the role of heparan sulfate, integrins, and the signaling molecule FAK in HPV16 infection of human adult keratinocytes cell line (HaCaTs). Our data demonstrate that infection requires the binding of viral particles to heparan sulfate followed by activation of focal adhesion kinase through an integrin. Infections were reduced in the presence of the FAK inhibitor, TAE226. TAE226 was observed to inhibit viral entry to the early endosome a known infectious route. These findings suggest that FAK can serve as a novel target for antiviral therapy. PMID:20441998
Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway.
Digiacomo, Graziana; Tusa, Ignazia; Bacci, Marina; Cipolleschi, Maria Grazia; Dello Sbarba, Persio; Rovida, Elisabetta
2017-07-04
Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and β1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.
Akakura, Shin; Bouchard, Rene; Bshara, Wiam; Morrison, Carl; Gelman, Irwin H.
2011-01-01
The ability of SSeCKS/Gravin/AKAP12 (SSeCKS) to negatively regulate cell cycle progression is thought to relate to its spatiotemporal scaffolding activity for key signaling molecules such as protein kinase A and C, calmodulin, and cyclins. SSeCKS is downregulated upon progression to malignancy in many cancer types, including melanoma and non-melanoma skin cancer. The forced re-expression of SSeCKS is especially potent in suppressing metastasis through the inhibition of VEGF-mediated neovascularization. We have previously shown that SSeCKS-null (KO) mice exhibit hyperplasia and focal dysplasia in the prostate marked by activated Akt. To address whether KO-mice exhibit increased skin carcinogenesis, WT and KO C57BL/6 mice were treated topically with 12-O-tetradecanoylphorbol-13-acetate and 7,12-dimethylbenzanthracene. Compared to WT mice, KO mice developed squamous papillomas more rapidly and in greater numbers, and also exhibited significantly increased progression to squamous cell carcinoma. Untreated KO epidermal layers were thicker than those in age-matched WT mice, and exhibited significantly increased levels of FAK and phospho-ERK1/2, known mediators of carcinogen-induced squamous papilloma progression to carcinoma. Compared to protein levels in WT mouse embryo fibroblasts (MEF), SSeCKS levels were increased in FAK-null cells whereas FAK levels were increased in SSeCKS-null cells. RNAi studies in WT MEF cells suggest that SSeCKS and FAK attenuate each other’s expression. Our study implicates a role for SSeCKS in preventing of skin cancer progression possibly through negatively regulating FAK expression. PMID:21128249
Benzina, Sami; Harquail, Jason; Guerrette, Roxann; O'Brien, Pierre; Jean, Stéphanie; Crapoulet, Nicolas; Robichaud, Gilles A.
2016-01-01
The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression. PMID:28070224
Tsuda, T; Kusui, T; Jensen, R T
1997-12-23
Recent studies show that tyrosine phosphorylation by a number of neuropeptides may be an important intracellular pathway in mediating changes in cell function, particularly related to growth. Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action. In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides. NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells. NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP). The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells. TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB. A23187 potentiated the effect of TPA. Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation. Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X. The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%. However, tyrphostin A25 did not inhibit NMB-stimulated increases in [3H]inositol phosphates. Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely. In contrast, colchicine, an agent which
Alt-Holland, Addy; Sowalsky, Adam; Szwec-Levin, Yonit; Shamis, Yulia; Hatch, Harold; Feig, Larry A.; Garlick, Jonathan A.
2011-01-01
Advanced stages of epithelial carcinogenesis involve the loss of intercellular adhesion, but it remains unclear how proteins that regulate alterations in cell-cell and cell-matrix adhesion are deregulated to promote the early stages of cancer development. To address this, a three-dimensional human tissue model that mimics the incipient stages of Squamous Cell Carcinoma (SCC) was used to study how E-cadherin suppression promotes tumor progression in Ras-expressing human keratinocytes. We found that E-cadherin suppression triggered elevated mRNA and protein expression levels of Focal Adhesion Kinase (FAK), and increased FAK and Src activities above the level seen in Ras-expressing E-cadherin-competent keratinocytes. sh-RNA-mediated depletion of FAK and Src restored E-cadherin expression levels by increasing its stability in the membrane, and blocked tumor cell invasion in tissues. Surface transplantation of these tissues to mice resulted in reversion of the tumor phenotype to low-grade tumor islands in contrast to control tissues that manifested an aggressive, high-grade SCC. These findings suggest that the tumor-promoting effect of E-cadherin suppression, a common event in SCC development, is exacerbated by enhanced E-cadherin degradation induced by elevated FAK and Src activities. Furthermore, they imply that targeting FAK or Src in human epithelial cells with neoplastic potential may inhibit the early stages of SCC. PMID:21716326
Bikis, Christos; Moris, Demetrios; Vasileiou, Ioanna; Patsouris, Eustratios; Theocharis, Stamatios
2015-04-01
The focal adhesion kinase (FAK) and the Src families of kinases are subfamilies of the non-receptor protein tyrosine kinases. FAK activity is regulated by gene amplification, alternative splicing and phosporylation/dephosphorylation. FAK/Src complex has been found to participate through various pathways in neuronal models of ischemia-reperfusion injury (IRI) with conflicting results. The aim of the present review is to summarize the currently available data on this subject. The MEDLINE/PubMed database was searched for publications with the medical subject heading IRI and FAK and/or Src, nervous system. We restricted our search till 2014. We identified 93 articles that were available in English as abstracts or/and full-text articles that were deemed appropriate for our review. FAK has been found to have a beneficial preconditioning effect on IRI through activation via the protein kinase C (PKC) pathway by anesthetic agents. Of great importance are the interactions between FAK/Src and VEGF that has been already detected as a protective mean for IRI. The effect of VEGF administration might depend on dose as well as on time of administration. A Ca(2+)/calmodulin-dependent protein kinase II or PKC inhibitors seem to have protective effects on IRI by inhibiting ion channels activation.
Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.
2014-01-01
Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733
2009-12-10
sites of integrin-clustering that link the actin cytoskeleton to the extracellular matrix (ECM; (Burridge et al., 1988)). The primary functions of...Hall, 1992). Furthermore, in fibroblasts, focal adhesion kinase (FAK), a key FA signaling molecule, is necessary for mechanosensing (Geiger et al...promotes FAK activation through phosphorylation on Y397 and Y925, followed by FAK- dependent extracellular signal-regulated kinase (ERK) phosphorylation
Yuan, Cheng; Gou, Xiaoli; Deng, Jiang; Dong, Zhijun; Ye, Peng; Hu, Zhenming
2018-06-14
Adipose derived stem cells (ADSCs) could undergo osteogenesis via focal adhesion kinase (FAK) and bone morphogenetic protein (BMP) 9 signals, both of which could affect Wnt-β-catenin signal, a signal pathway closely related to ADSCs osteogenesis. It's still enigma whether FAK and BMP-9 contribute to osteogenesis. Here, we examined the effect of FAK on BMP9-inducedosteogenic differentiation, unveiled the possible molecular mechanism underling this process. In the present study, ADSCs were isolated and purified, and cells of passage 3 underwent virus mediated transfection to prepare ADSCs with stable FAK shRNA expression. Cell viability and migration were detected by MTT and transwell assay, respectively. Expression of osteogenic gene, phosphorylation of FAK and GSK were detected by western blot. Osteogenic potential was evaluated by activity of alkaline phosphatase (ALP) and calcium deposition by ALP staining and Alizarin Red S staining. BMP-9 administration promoted ADSCs osteogenesis. Knocking down FAK attenuated this process, inhibited osteogenic proteins expression through Wnt-β-catenin signal. BMP-9 also triggered ADSCs proliferation and migration, and shFAK antagonized such effects too. Although Wnt signal is affected by FAK shRNA, Smad signal remains intact in ADSCs with shFAK. FAK and BMP-9 could cross talk on Wnt signal pathway and promote ADSCs osteogenesis. FAK could participate in BMP-9 induced ADSCs osteogenesis via Wnt signal pathway other than Smads signals (see in graph). Copyright © 2018. Published by Elsevier Masson SAS.
Anderson, Hannah J; Galileo, Deni S
2016-06-01
The cell adhesion/recognition protein L1CAM (L1; CD171) has previously been shown to act through integrin, focal adhesion kinase (FAK) and fibroblast growth factor receptor (FGFR) signaling pathways to increase the motility and proliferation of glioblastoma cells in an autocrine/paracrine manner. Here, we investigated the effects of clinically relevant small-molecule inhibitors of the integrin, FAK and FGFR signaling pathways on glioblastoma-derived cells to determine their effectiveness and selectivity for diminishing L1-mediated stimulation. The effects of the FGFR inhibitor PD173074, the FAK inhibitors PF431396 and Y15 and the αvβ3/αvβ5 integrin inhibitor cilengitide were assessed in L1-positive and L1-negative variants of the human glioblastoma-derived cell lines T98G and U-118 MG. Their motility and proliferation were quantified using time-lapse microscopy and DNA content/cell cycle analyses, respectively. The application of all four inhibitors resulted in reductions in L1-mediated motility and proliferation rates of L1-positive glioblastoma-derived cells, down to the level of L1-negative cells when used at nanomolar concentrations, whereas no or much smaller reductions in these rates were obtained in L1-negative cells. In addition, we found that single inhibitor treatment resulted in maximum effects (i.e., combinations of FAK or integrin inhibitors with the FGFR inhibitor were rarely more effective). These results suggest that FAK may act as a point of convergence between the integrin and FGFR signaling pathways stimulated by L1 in these cells. We here show for the first time that small-molecule inhibitors of FGFR, integrins and FAK effectively and selectively abolish L1-stimulated migration and proliferation of glioblastoma-derived cells. Our results suggest that these inhibitors have the potential to reduce the aggressiveness of high-grade gliomas expressing L1.
Swaminathan, Vinay; Fischer, R S; Waterman, Clare M
2016-04-01
Cell migration is initiated in response to biochemical or physical cues in the environment that promote actin-mediated lamellipodial protrusion followed by the formation of nascent integrin adhesions (NAs) within the protrusion to drive leading edge advance. Although FAK is known to be required for cell migration through effects on focal adhesions, its role in NA formation and lamellipodial dynamics is unclear. Live-cell microscopy of FAK(-/-)cells with expression of phosphorylation deficient or a FERM-domain mutant deficient in Arp2/3 binding revealed a requirement for FAK in promoting the dense formation, transient stabilization, and timely turnover of NA within lamellipodia to couple actin-driven protrusion to adhesion and advance of the leading edge. Phosphorylation on Y397 of FAK promotes dense NA formation but is dispensable for transient NA stabilization and leading edge advance. In contrast, transient NA stabilization and advance of the cell edge requires FAK-Arp2/3 interaction, which promotes Arp2/3 localization to NA and reduces FAK activity. Haptosensing of extracellular matrix (ECM) concentration during migration requires the interaction between FAK and Arp2/3, whereas FAK phosphorylation modulates mechanosensing of ECM stiffness during spreading. Taken together, our results show that mechanistically separable functions of FAK in NA are required for cells to distinguish distinct properties of their environment during migration. © 2016 Swaminathan et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Focal adhesion kinase (FAK) perspectives in mechanobiology: implications for cell behaviour.
Tomakidi, Pascal; Schulz, Simon; Proksch, Susanne; Weber, Wilfried; Steinberg, Thorsten
2014-09-01
Mechanobiology is a scientific interface discipline emerging from engineering and biology. With regard to tissue-regenerative cell-based strategies, mechanobiological concepts, including biomechanics as a target for cell and human mesenchymal stem cell behaviour, are on the march. Based on the periodontium as a paradigm, this mini-review discusses the key role of focal-adhesion kinase (FAK) in mechanobiology, since it is involved in mediating the transformation of environmental biomechanical signals into cell behavioural responses via mechanotransducing signalling cascades. These processes enable cells to adjust quickly to environmental cues, whereas adjustment itself relies on the specific intramolecular phosphorylation of FAK tyrosine residues and the multiple interactions of FAK with distinct partners. Furthermore, interaction-triggered mechanotransducing pathways govern the dynamics of focal adhesion sites and cell behaviour. Facets of behaviour not only include cell spreading and motility, but also proliferation, differentiation and apoptosis. In translational terms, identified and characterized biomechanical parameters can be incorporated into innovative concepts of cell- and tissue-tailored clinically applied biomaterials controlling cell behaviour as desired.
Germline deletion of FAK-related non-kinase delays post-natal cardiomyocyte mitotic arrest
O’Neill, Thomas J.; Mack, Christopher P.; Taylor, Joan M.
2012-01-01
The cardiomyocyte phenotypic switch from a proliferative to terminally differentiated state impacts normal heart development and pathologic myocardial remodeling, yet the signaling mechanisms that regulate this vital process are incompletely understood. Studies from our lab and others indicate that focal adhesion kinase (FAK) is a critical regulator of cardiac growth and remodeling and we found that expression of the endogenous FAK inhibitor, FAK-related non kinase (FRNK) coincided with postnatal cardiomyocyte arrest. Mis-expression of FRNK in the embryonic heart led to pre-term lethality associated with reduced cardiomyocyte proliferation and led us to speculate that the postnatal FRNK surge might be required to promote quiescence in this growth promoting environment. Herein, we provide strong evidence that endogenous FRNK contributes to post-mitotic arrest. Depletion of FRNK promoted DNA synthesis in post-natal day (P) 10 hearts accompanied by a transient increase in DNA content and multi-nucleation by P14, indicative of DNA replication without cell division. Interestingly, a reduction in tri- and tetra-nucleated cardiomyocytes, concomitant with an increase in bi-nucleated cells by P21, indicated the possibility that FRNK-depleted cardiomyocytes underwent eventual cytokinesis. In support of this conclusion, Aurora B-labeled central spindles (a hallmark of cytokinesis) were observed in tetra-nucleated P20 FRNK−/− but not wt cardiomyocytes, while no evidence of apoptosis was observed. Moreover, hearts from FRNK null mice developed ventricular enlargement that persisted until young adulthood which resulted from myocyte expansion rather than myocyte hypertrophy or interstitial growth. These data indicate that endogenous FRNK serves an important role in limiting DNA synthesis and regulating the un-coupling between DNA synthesis and cytokinesis in the post-natal myocardium. PMID:22555221
Chang, Hung-Ming; Shyu, Ming-Kwang; Tseng, Guo-Fang; Liu, Chiung-Hui; Chang, Hung-Shuo; Lan, Chyn-Tair; Hsu, Wen-Ming; Liao, Wen-Chieh
2013-01-01
Background Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches. Methodology and Principal Findings Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles. Conclusions As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI. PMID:23301073
Bjerke, Maureen A.; Dzamba, Bette; Wang, Chong; DeSimone, Douglas W.
2014-01-01
Collective cell movements are integral to biological processes such as embryonic development and wound healing and also have a prominent role in some metastatic cancers. In migrating Xenopus mesendoderm, traction forces are generated by cells through integrin-based adhesions and tension transmitted across cadherin adhesions. This is accompanied by assembly of a mechanoresponsive cadherin adhesion complex containing keratin intermediate filaments and the catenin-family member plakoglobin. We demonstrate that focal adhesion kinase (FAK), a major component of integrin adhesion complexes, is required for normal morphogenesis at gastrulation, closure of the anterior neural tube, axial elongation and somitogenesis. Depletion of zygotically expressed FAK results in disruption of mesendoderm tissue polarity similar to that observed when expression of keratin or plakoglobin is inhibited. Both individual and collective migrations of mesendoderm cells from FAK depleted embryos are slowed, cell protrusions are disordered, and cell spreading and traction forces are decreased. Additionally, keratin filaments fail to organize at the rear of cells in the tissue and association of plakoglobin with cadherin is diminished. These findings suggest that FAK is required for the tension-dependent assembly of the cadherin adhesion complex that guides collective mesendoderm migration, perhaps by modulating the dynamic balance of substrate traction forces and cell cohesion needed to establish cell polarity. PMID:25127991
Li, Wen-Xue; Chen, Li-Ping; Sun, Min-Ying; Li, Jun-Tao; Liu, Hua-Zhang; Zhu, Wei
2015-01-01
Late stage hepatocellular carcinoma (HCC) usually has a low survival rate because it has high potential of metastases and there is no effective cure. 3′3-Diindolylmethane (DIM) is the major product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables. DIM has been proved to exhibit anticancer properties. In this study, we explored the effects and molecular mechanisms of anti-metastasis of DIM on HCC cells both in vitro and in vivo. We chose two HCC cell lines SMMC-7721 and MHCC-97H that have high potential of invasion. The results showed that DIM inhibited the proliferation, migration and invasion of these two cell lines in vitro. In addition, in vivo study demonstrated that DIM significantly decreased the volumes of SMMC-7721 orthotopic liver tumor and suppressed lung metastasis in nude mice. Focal Adhesion Kinase (FAK) is found over activated in HCC cells. We found that DIM decreased the level of phospho-FAK (Tyr397) both in vitro and in vivo. DIM inhibition of phospho-FAK (Tyr397) led to down-regulation of MMP2/9 and decreased potential of metastasis. DIM also repressed the migration and invasion induced by vitronectin through inactivation of FAK pathway and down-regulation of MMP2/9 in vitro. We also found that pTEN plays a role in down-regulation of FAK by DIM. These results demonstrated that DIM blocks HCC cell metastasis by suppressing tumor cell migration and invasion. The anti-metastasis effect of DIM could be explained to be its down-regulated expression and activation of MMP2/9 partly induced by up-regulation of pTEN and inhibition of phospho-FAK (Tyr397). PMID:26068982
Cavazzoni, Andrea; La Monica, Silvia; Alfieri, Roberta; Ravelli, Andrea; Van Der Steen, Nele; Sciarrillo, Rocco; Madeddu, Denise; Lagrasta, Costanza Anna Maria; Quaini, Federico; Bonelli, Mara; Fumarola, Claudia; Cretella, Daniele; Digiacomo, Graziana; Tiseo, Marcello; Peters, Godefridus J.; Ardizzoni, Andrea; Petronini, Pier Giorgio; Giovannetti, Elisa
2017-01-01
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib. An increase in AKT and FAK phosphorylation, associated with increased proliferation and invasiveness, paralleled by the acquisition of mesenchymal markers, and overexpression of the oncomir miR-21 were observed in SKMES-1-derived cell clones with a stable reduction of PTEN. Notably, the combined treatment induced a synergistic inhibition of cell proliferation, and a significant reduction in cell migration and invasion only in cells with reduced PTEN. The molecular mechanisms underlying these findings were unraveled using a specific RTK array that showed a reduction in phosphorylation of key kinases such as JNK, GSK-3 α/β, and AMPK-α2, due to the concomitant decrease in AKT and FAK activation. In conclusion, the combination of buparlisib and defactinib was effective against cells with reduced PTEN and warrants further studies as a novel therapeutic strategy for stage IV SCC patients with loss of PTEN expression. PMID:28881794
L1 stimulation of human glioma cell motility correlates with FAK activation
Yang, Muhua; Li, Yupei; Chilukuri, Kalyani; Brady, Owen A.; Boulos, Magdy I.; Kappes, John C.
2011-01-01
The neural adhesion/recognition protein L1 (L1CAM; CD171) has been shown or implicated to function in stimulation of cell motility in several cancer types, including high-grade gliomas. Our previous work demonstrated the expression and function of L1 protein in stimulation of cell motility in rat glioma cells. However, the mechanism of this stimulation is still unclear. This study further investigated the function of L1 and L1 proteolysis in human glioblastoma multiforme (GBM) cell migration and invasion, as well as the mechanism of this stimulation. L1 mRNA was found to be present in human T98G GBM cell line but not in U-118 MG grade III human glioma cell line. L1 protein expression, proteolysis, and release were found in T98G cells and human surgical GBM cells by Western blotting. Exosome-like vesicles released by T98G cells were purified and contained full-length L1. In a scratch assay, T98G cells that migrated into the denuded scratch area exhibited upregulation of ADAM10 protease expression coincident with loss of surface L1. GBM surgical specimen cells exhibited a similar loss of cell surface L1 when xenografted into the chick embryo brain. When lentivirally introduced shRNA was used to attenuate L1 expression, such T98G/shL1 cells exhibited significantly decreased cell motility by time lapse microscopy in our quantitative Super Scratch assay. These cells also showed a decrease in FAK activity and exhibited increased focal complexes. L1 binding integrins which activate FAK were found in T98G and U-118 MG cells. Addition of L1 ectodomain-containing media (1) rescued the decreased cell motility of T98G/shL1 cells and (2) increased cell motility of U-118 MG cells but (3) did not further increase T98G cell motility. Injection of L1-attenuated T98G/shL1 cells into embryonic chick brains resulted in the absence of detectable invasion compared to control cells which invaded brain tissue. These studies support a mechanism where glioma cells at the edge of a cell mass
L1 stimulation of human glioma cell motility correlates with FAK activation.
Yang, Muhua; Li, Yupei; Chilukuri, Kalyani; Brady, Owen A; Boulos, Magdy I; Kappes, John C; Galileo, Deni S
2011-10-01
The neural adhesion/recognition protein L1 (L1CAM; CD171) has been shown or implicated to function in stimulation of cell motility in several cancer types, including high-grade gliomas. Our previous work demonstrated the expression and function of L1 protein in stimulation of cell motility in rat glioma cells. However, the mechanism of this stimulation is still unclear. This study further investigated the function of L1 and L1 proteolysis in human glioblastoma multiforme (GBM) cell migration and invasion, as well as the mechanism of this stimulation. L1 mRNA was found to be present in human T98G GBM cell line but not in U-118 MG grade III human glioma cell line. L1 protein expression, proteolysis, and release were found in T98G cells and human surgical GBM cells by Western blotting. Exosome-like vesicles released by T98G cells were purified and contained full-length L1. In a scratch assay, T98G cells that migrated into the denuded scratch area exhibited upregulation of ADAM10 protease expression coincident with loss of surface L1. GBM surgical specimen cells exhibited a similar loss of cell surface L1 when xenografted into the chick embryo brain. When lentivirally introduced shRNA was used to attenuate L1 expression, such T98G/shL1 cells exhibited significantly decreased cell motility by time lapse microscopy in our quantitative Super Scratch assay. These cells also showed a decrease in FAK activity and exhibited increased focal complexes. L1 binding integrins which activate FAK were found in T98G and U-118 MG cells. Addition of L1 ectodomain-containing media (1) rescued the decreased cell motility of T98G/shL1 cells and (2) increased cell motility of U-118 MG cells but (3) did not further increase T98G cell motility. Injection of L1-attenuated T98G/shL1 cells into embryonic chick brains resulted in the absence of detectable invasion compared to control cells which invaded brain tissue. These studies support a mechanism where glioma cells at the edge of a cell mass
SASH1 inhibits cervical cancer cell proliferation and invasion by suppressing the FAK pathway.
Chen, Hui; Wang, Dongliang; Liu, Yuling
2016-04-01
SAM and SH3 domain containing 1 (SASH1), a member of the SLY-family of signal adapter proteins, is a candidate tumor suppressor in several types of cancer. However, the role of SASH1 in cervical cancer remains to be elucidated. Therefore, in the present study, the role of SASH1 in cervical cancer and the underlying mechanism was investigated. Cell proliferation was detected by the MTT assay. Cell invasion was measured by Transwell assay. The mRNA expression levels of SASH1, matrix metalloproteinase (MMP)‑2 and MMP‑9 were determined by reverse transcription quantitative polymerase chain reaction. The protein expression levels of SASH1, MMP‑2, MMP‑9 and focal adhesion kinase (FAK) were determined by western blot analysis. The results demonstrated that SASH1 was downregulated in cervical cancer tissues and cell lines. Subsequently, a vector that overexpresses SASH1 was constructed. Overexpression of SASH1 was found to significantly inhibit cervical cancer cell proliferation and invasion, and also significantly reduce the expression of MMP‑2 and MMP‑9 in cancer cells. In addition, SASH1 modulated the FAK signaling pathway. Overexpression of SASH1 suppressed the expression of FAK in cancer cells. Taken together, the results suggested that SASH1 inhibits cervical cancer cell proliferation and invasion by suppressing the FAK pathway.
Aulakh, Gurpreet K; Petri, Björn; Wojcik, Katarzyna M; Colarusso, Pina; Lee, James J; Patel, Kamala D
2018-04-06
Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. ©2018 Society for Leukocyte Biology.
Portillo, Jose-Andres C; Muniz-Feliciano, Luis; Lopez Corcino, Yalitza; Lee, So Jung; Van Grol, Jennifer; Parsons, Sarah J; Schiemman, William P; Subauste, Carlos S
2017-10-01
Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling. FAK caused activation of Src that in turn mediated Epidermal Growth Factor Receptor (EGFR) phosphorylation at the unique Y845 residue. Expression of Src-resistant Y845F EGFR mutant markedly inhibited ROP16-independent activation of STAT3 in host cells. Activation of FAK, Y845 EGFR or STAT3 prevented activation of PKR and eIF2α, key stimulators of autophagy. Genetic or pharmacologic inhibition of FAK, Src, EGFR phosphorylation at Y845, or STAT3 caused accumulation of the autophagy protein LC3 and LAMP-1 around the parasite and parasite killing dependent on autophagy proteins (ULK1 and Beclin 1) and lysosomal enzymes. Parasite killing was inhibited by expression of dominant negative PKR. Thus, T. gondii activates a FAK→Src→Y845-EGFR→STAT3 signaling axis within mammalian cells, thereby enabling the parasite to survive by avoiding autophagic targeting through a mechanism likely dependent on preventing activation of PKR and eIF2α.
Ma, Dandan; Kou, Xiaoxing; Jin, Jing; Xu, Taotao; Wu, Mengjie; Deng, Liquan; Fu, Lusi; Liu, Yi; Wu, Gang; Lu, Haiping
2016-11-07
Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal-regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin β1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin β1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway.
Ma, Dandan; Kou, Xiaoxing; Jin, Jing; Xu, Taotao; Wu, Mengjie; Deng, Liquan; Fu, Lusi; Liu, Yi; Wu, Gang; Lu, Haiping
2016-01-01
Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal–regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin β1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin β1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway. PMID:27827993
Hwang, Jung Seok; Eun, So Young; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Paek, Kyung Shin; Do, Jeong Tae; Lim, Dae-Seog; Seo, Han Geuk
2015-05-01
The peroxisome proliferator-activated receptor delta (PPARδ) has been implicated in the modulation of vascular homeostasis. However, its roles in the apoptotic cell death of vascular smooth muscle cells (VSMCs) are poorly understood. Here, we demonstrate that PPARδ modulates oxidized low-density lipoprotein (oxLDL)-induced apoptosis of VSMCs through the transforming growth factor-β (TGF-β) and focal adhesion kinase (FAK) signaling pathways. Activation of PPARδ by GW501516, which is a specific ligand, significantly inhibited oxLDL-induced cell death and generation of reactive oxygen species in VSMCs. These inhibitory effects were significantly reversed in the presence of small interfering (si)RNA against PPARδ, or by blockade of the TGF-β or FAK signaling pathways. Furthermore, PPARδ-mediated recovery of FAK phosphorylation suppressed by oxLDL was reversed by SB431542, a specific ALK5 receptor inhibitor, indicating that a TGF-β/FAK signaling axis is involved in the action of PPARδ. Among the protein kinases activated by oxLDL, p38 mitogen-activated protein kinase was suppressed by ligand-activated PPARδ. In addition, oxLDL-induced expression and translocation of pro-apoptotic or anti-apoptotic factors were markedly affected in the presence of GW501516. Those effects were reversed by PPARδ siRNA, or inhibitors of TGF-β or FAK, which also suggests that PPARδ exerts its anti-apoptotic effect via a TGF-β/FAK signaling axis. Taken together, these findings indicate that PPARδ plays an important role in the pathophysiology of disease associated with apoptosis of VSMC, such as atherosclerosis and restanosis. Copyright © 2015 Elsevier Ltd. All rights reserved.
Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer.
Joshi, Suhasini; Cruz, Eric; Rachagani, Satyanarayana; Guha, Sushovan; Brand, Randall E; Ponnusamy, Moorthy P; Kumar, Sushil; Batra, Surinder K
2016-08-01
The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. Similarly, an elevated BA levels was observed in pancreatic juice derived from PC patients (p < 0.05) than non-pancreatic non-healthy (NPNH) controls, further establishing the clinical association of BA with the pathogenesis of PC. The tumor-promoting functions of BA were established by observed transcriptional upregulation of oncogenic MUC4 expression. Luciferase reporter assay revealed distal MUC4 promoter as the primary responsive site to BA. In silico analysis recognized two c-Jun binding sites at MUC4 distal promoter, which was biochemically established using ChIP assay. Interestingly, BA treatment led to an increased transcription and activation of c-Jun in a FAK-dependent manner. Additionally, BA receptor, namely FXR, which is also upregulated at transcriptional level in PC patient samples, was demonstrated as an upstream molecule in BA-mediated FAK activation, plausibly by regulating Src activation. Altogether, these results demonstrate that elevated levels of BA increase the tumorigenic potential of PC cells by inducing FXR/FAK/c-Jun axis to upregulate MUC4 expression, which is overexpressed in pancreatic tumors and is known to be associated with progression and metastasis of PC. Published by Elsevier B.V.
Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound
Mehić, Edin; Xu, Julia M.; Caler, Connor J.; Coulson, Nathaniel K.; Moritz, Chet T.; Mourad, Pierre D.
2014-01-01
Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250–700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1–10 W/cm2. That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, ‘modulated’ means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU’s ability to produce compact sources of ultrasound at the very low frequencies (10–100s of Hertz) that are commensurate with the natural frequencies of the brain. PMID:24504255
Rosso, Francesco; Marino, Gerardo; Muscariello, Livio; Cafiero, Gennaro; Favia, Pietro; D'Aloia, Erica; d'Agostino, Riccardo; Barbarisi, Alfonso
2006-06-01
We used combined plasma-deposition process to deposit smooth and nanostructured fluorocarbon coatings on polyethylenethereftalate (PET) substrates, to obtain surfaces with identical chemical composition and different roughness, and investigate the effect of surface nanostructures on adhesion and proliferation of 3T3 Swiss Albino Mouse fibroblasts. Untreated PET and polystyrene (PS) were used as controls for cell culture. We have found that the statistically significant increase of cell proliferation rate and FAK (a nonreceptor tyrosine kinase) activation detected on ROUGH fluorocarbon surfaces is due to the presence of nanostructures. Changes in cytoskeletal organization and phospho FAK (tyr 397) localization were evident after 60 min on cells adhering to ROUGH surfaces. This change was characterized by the formation of actin stress fibers along lamellar membrane protrusion instead of usual focal contacts. Also the morphology of the adhering fibroblasts (60 min) adhering on ROUGH surfaces was found quite different compared to cells adhering on smooth ones. Copyright 2006 Wiley-Liss, Inc.
Stagno, Matias Julian; Zacharopoulou, Nefeli; Bochem, Jonas; Tsapara, Anna; Pelzl, Lisann; Al-Maghout, Tamer; Kallergi, Galatea; Alkahtani, Saad; Alevizopoulos, Konstantinos; Dimas, Konstantinos; Calogeropoulou, Theodora; Warmann, Steven W; Lang, Florian; Schmid, Evi; Stournaras, Christos
2017-01-01
Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells. Migration was assessed by transwell and wound healing assays, Orai1 and Stim1 abundance by RT-PCR and confocal immunofluorescence microscopy, Fura-2 fluorescence was utilized to determine intracellular Ca2+ and Western blotting for FAK/pFAK measurements. We observed strong inhibition of cell migration in istaroxime treated DU-145 prostate cancer cells. Istaroxime further decreased Orai1 and Stim1 transcript levels and downregulated Orai1 protein expression. Moreover, SOCE was significantly decreased upon istaroxime treatment. Furthermore, istaroxime strikingly diminished phosphorylated FAK levels. Interestingly, the efficacy of istaroxime on the inhibition of DU-145 cell migration was further enhanced by blocking Orai1 with 2-APB and FAK with the specific inhibitor PF-00562271. These results provide strong evidence that istaroxime prevents cell migration and motility of DU-145 prostate tumor cells, an effect at least partially attributed to Orai1 downregulation and FAK de-activation. Collectively our results indicate that this enzyme inhibitor, besides its pro-apoptotic action, affects motility of cancer cells, supporting its potential role as a strong candidate for further clinical cancer drug development. © 2017 The Author(s). Published by S. Karger AG, Basel.
Sun, Jinghui; Luo, Qing; Liu, Lingling; Song, Guanbin
2018-07-28
Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively. We found that 2 dyne/cm 2 shear stress loading for 6 h promotes LCSC migration and activation of the FAK and ERK1/2 signalling pathways, whereas treatment with the FAK phosphorylation inhibitor PF573228 or the ERK1/2 phosphorylation inhibitor PD98059 suppressed the shear stress-promoted migration, indicating the involvement of FAK and ERK1/2 activation in shear stress-induced LCSC migration. Additionally, atomic force microscopy (AFM) analysis showed that shear stress lowers LCSC stiffness via the FAK and ERK1/2 pathways, suggesting that the mechanism by which shear stress promotes LCSC migration might partially be responsible for the decrease in cell stiffness. Further experiments focused on the role of the actin cytoskeleton, demonstrating that the F-actin filaments in LCSCs are less well-defined after shear stress treatment, providing an explanation for the reduction in cell stiffness and the promotion of cell migration. Overall, our study demonstrates that shear stress promotes LCSC migration through the activation of the FAK-ERK1/2 signalling pathways, which further results in a reduction of organized actin and softer cell bodies. Copyright © 2018 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Miao, Lei; Xin, Xiaoming; Xin, Hong; Shen, Xiaoyan; Zhu, Yi-Zhun
2016-03-01
Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK397, and -FAK925. Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.
Luo, Man-Li; Zhou, Zhuan; Sun, Lichao; Yu, Long; Sun, Lixin; Liu, Jun; Yang, Zhihua; Ran, Yuliang; Yao, Yandan; Hu, Hai
2018-05-28
Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. Immunohistochemistry revealed that the ADAM12-L was overexpressed in human ESCC tissues, especially at cancer invasive edge, and ADAM12-L overexpression tightly correlated with increased metastasis and poor outcome of ESCC patients. Indeed, ADAM12-L knockdown reduced the invasion and metastasis of ESCC cells both in vitro and in vivo. Furthermore, we demonstrated that ADAM12-L participated in focal adhesion turnover and promoted the activation of focal adhesion kinase (FAK), which in turn increased ADAM12-L transcription through FAK/JNK/c-Jun axis. Therefore, a loop initiated from the cancer cell upon the engagement with extracellular matrix through FAK and c-Jun to enhance ADAM12-L expression is established, leading to the positive feedback of further FAK activation and prompting metastasis. Our study indicates that overexpression of ADAM12-L can serve as a precision marker to determine the activation of this loop. Targeting ADAM12-L to disrupt this positive feedback loop represents a promising strategy to treat the metastasis of esophageal cancers. Copyright © 2018 Elsevier B.V. All rights reserved.
Shen, Yang; Wang, Guixue; Huang, Xianliang; Zhang, Qin; Wu, Jiang; Tang, Chaojun; Yu, Qingsong; Liu, Xiaoheng
2012-01-01
Vascular endothelial cell (EC) adhesion and migration are essential processes in re-endothelialization of implanted biomaterials. There is no clear relationship and mechanism between EC adhesion and migration behaviour on surfaces with varying wettabilities. As model substrates, plasma SiOx:H nanocoatings with well-controlled surface wettability (with water contact angles in the range of 98.5 ± 2.3° to 26.3 ± 4.0°) were used in this study to investigate the effects of surface wettability on cell adhesion/migration and associated protein expressions in FAK-Rho GTPases signalling pathways. It was found that EC adhesion/migration showed opposite behaviour on the hydrophilic and hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397 site of FAK could significantly inhibit cell adhesion/migration, suggesting that EC adhesion and migration on surfaces with different wettabilities involve (p)FAK and its downstream signalling pathways. Western blot results suggested that the FAK-Rho GTPases signalling pathways were correlative to EC migration on hydrophobic plasma SiOx:H surfaces, but uncertain to hydrophilic surfaces. This work demonstrated that surface wettability could induce cellular behaviours that were associated with different cellular signalling events. PMID:21715399
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, I-Hua; Shih, Hsin-Chu; Hsieh, Pei-Wen
Anoikis is defined as apoptosis, which is induced by inappropriate cell–matrix interactions. Cancer cells with anoikis resistance tend to undergo metastasis, and this phenomenon has been reported to be associated with integrin and FAK activity. HPW-RX40 is a derivative of 3,4-methylenedioxy-β-nitrostyrene, which is known to prevent platelet aggregation by inhibition of integrin. In the present study, we investigated the effect of HPW-RX40 on an anoikis-resistant human breast cancer cell line MDA-MB-231. HPW-RX40 inhibited cell aggregation and induced cell death in suspending MDA-MB-231 cells, but had only little effect on the monolayer growth of adherent cells. Analysis of caspase activation andmore » poly (ADP-ribose) polymerase (PARP) cleavage confirmed anoikis in HPW-RX40-treated suspending cancer cells. HPW-RX40 also affected the Bcl-2 family proteins in detached cancer cells. Furthermore, HPW-RX40 inhibited detachment-induced activation of FAK and the downstream phosphorylation of Src and paxillin, but did not affect this pathway in adherent cancer cells. We also found that the expression and activation of β1 integrin in MDA-MB-231 cells were reduced by HPW-RX40. The combination of HPW-RX40 with an EGFR inhibitor led to enhanced anoikis and inhibition of the FAK pathway in breast cancer cells. Taken together, our results suggest that HPW-RX40 restores the anoikis sensitivity in the metastatic breast cancer cells by inhibiting integrin and subsequent FAK activation, and reveal a potential strategy for prevention of tumor metastasis. - Highlights: • The β-nitrostyrene derivative, HPW-RX40, induces anoikis in human breast cancer cells. • HPW-RX40 inhibits the integrin/FAK signaling pathway. • The combination of HPW-RX40 with an EGFR inhibitor leads to enhanced anoikis. • HPW-RX40 may have a potential to prevent the spread of metastatic breast cancer.« less
2014-01-01
Background Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. Results FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCϒ, NWASP, ARP2/3, and ROCK had no influence this. Conclusions FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies. PMID:24885257
Jia, Jun; Martin, Tracey Amanda; Ye, Lin; Jiang, Wen Guo
2014-05-21
Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCΥ, NWASP, ARP2/3, and ROCK had no influence this. FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies.
Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3 and KIT driven Leukemogenesis
Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H.; Waskow, Emily R.; Visconte, Valeria; Tiu, Ramon V.; Smith, Catherine C.; Shah, Neil; Bunting, Kevin D.; Boswell, H. Scott; Liu, Yan; Chan, Rebecca J.; Kapur, Reuben
2015-01-01
SUMMARY Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK), whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. PMID:25456130
miR-1298 inhibits mutant KRAS-driven tumor growth by repressing FAK and LAMB3
Zhou, Ying; Dang, Jason; Chang, Kung-Yen; Yau, Edwin; Aza-Blanc, Pedro; Moscat, Jorge; Rana, Tariq M.
2016-01-01
Global microRNA functional screens can offer a strategy to identify synthetic lethal interactions in cancer cells that might be exploited therapeutically. In this study, we applied this strategy to identify novel gene interactions in KRAS mutant cancer cells. In this manner, we discovered miR-1298, a novel miRNA that inhibited the growth of KRAS-driven cells both in vitro and in vivo. Using miR-TRAP affinity purification technology, we identified the tyrosine kinase FAK and the laminin subunit LAMB3 as functional targets of miR-1298. Silencing of FAK or LAMB3 recapitulated the synthetic lethal effects of miR-1298 expression in KRAS-driven cancer cells, whereas co-expression of both proteins was critical to rescue miR-1298-induced cell death. Expression of LAMB3 but not FAK was upregulated by mutant KRAS. In clinical specimens, elevated LAMB3 expression correlated with poorer survival in lung cancer patients with an oncogenic KRAS gene signature, suggesting a novel candidate biomarker in this disease setting. Our results define a novel regulatory pathway in KRAS-driven cancers which offers a potential therapeutic target for their eradication PMID:27698189
HAO, ZHENFENG; QIAN, JING; YANG, JISHI
2015-01-01
The present study identified that shikonin, a naphthoquinone extracted from the roots of Lithospermum erythrorhizon, inhibits the migration of ovarian cancer cells and induces their apoptosis by impairing the phosphorylation of two kinases, proto-oncogene tyrosine protein kinase Src (Src) and focal adhesion kinase (FAK). Ovarian carcinoma SKOV-3 cells were treated with various concentrations of shikonin and analyzed for the effects on cell migration, invasion and apoptosis via Transwell assays and flow cytometry. In addition, the effects of shikonin administration on the expression and phosphorylation of Src and FAK in the SKOV-3 cells were analyzed by western blotting. Shikonin appeared to induce apoptosis and decrease cell migration in the SKOV-3 ovarian cells. Furthermore, the present study provides evidence that shikonin may exert these effects on human ovarian carcinoma cells via the inhibition of the protein tyrosine kinases, Src and FAK. Thus, shikonin should be considered for additional investigation as a candidate agent for the prevention and treatment of human ovarian cancer. PMID:25621031
Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis.
Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H; Waskow, Emily R; Visconte, Valeria; Tiu, Ramon V; Smith, Catherine C; Shah, Neil; Bunting, Kevin D; Boswell, H Scott; Liu, Yan; Chan, Rebecca J; Kapur, Reuben
2014-11-20
Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Cheng, Peng; Li, Jiaojiao; Wang, Juan; Zhang, Xiaoyun; Zhai, Honglin
2018-05-01
Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in cancer cell migration, proliferation, and survival. To investigate the mechanism between FAK and triazinic inhibitors and design high activity inhibitors, a molecular modeling integrated with 3D-QSAR, molecular docking, molecular dynamics simulations, and binding free energy calculations was performed. The optimum CoMFA and CoMSIA models showed good reliability and satisfactory predictability (with Q 2 = 0.663, R 2 = 0.987, [Formula: see text] = 0.921 and Q 2 = 0.670, R 2 = 0.981, [Formula: see text] = 0.953). Its contour maps could provide structural features to improve inhibitory activity. Furthermore, a good consistency between contour maps, docking, and molecular dynamics simulations strongly demonstrates that the molecular modeling is reliable. Based on it, we designed several new compounds and their inhibitory activities were validated by the molecular models. We expect our studies could bring new ideas to promote the development of novel inhibitors with higher inhibitory activity for FAK.
Tsai, Wen-Chung; Yu, Tung-Yang; Lin, Li-Ping; Lin, Mioa-Sui; Tsai, Ting-Ta; Pang, Jong-Hwei S
2017-11-01
Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2506-2512, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Dao, Pascal; Jarray, Rafika; Le Coq, Johanne; Lietha, Daniel; Loukaci, Ali; Lepelletier, Yves; Hadj-Slimane, Réda; Garbay, Christiane; Raynaud, Françoise; Chen, Huixiong
2013-08-15
We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAK kinase domain is highly similar to that observed in the complex of TAE-226. Copyright © 2013 Elsevier Ltd. All rights reserved.
Pak, Jhang Ho; Bashir, Qudsia; Kim, In Ki; Hong, Sung-Jong; Maeng, Sejung; Bahk, Young Yil; Kim, Tong-Soo
2017-06-01
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion. In particular, the expression levels of integrin α isoforms and β4 were upregulated in response to ESPs. Increased expression of integrin β4 was probably correlated with activation of focal adhesion kinase (FAK) and the steroid receptor coactivator (Src) family kinase and the subsequent activation of two downstream focal adhesion molecules, paxillin and vinculin. Moreover, inhibition of FAK/Src activation reduced paxillin and vinculin phosphorylation and attenuated ESP-induced CCA cell migration and invasion. These findings suggest that the integrin β4-FAK/Src signaling axis may play a crucial role in clonorchiasis-associated CCA metastasis during tumor progression. Copyright © 2017 Elsevier B.V. All rights reserved.
Tsukamoto, Akira; Higashiyama, Satoru; Yoshida, Kenji; Watanabe, Yoshiaki; Furukawa, Katsuko S; Ushida, Takashi
2011-12-01
An increase in cytoplasmic calcium (Ca(2+) increase) is a second messenger that is often observed under ultrasound irradiation. We hypothesize that cavitation is a physical mechanism that underlies the increase in Ca(2+) in these experiments. To control the presence of cavitation, the wave type was controlled in a sonication chamber. One wave type largely contained a traveling wave (wave type A) while the other wave type largely contained a standing wave (wave type B). Fast Fourier transform (FFT) analysis of a sound field produced by the wave types ascertained that stable cavitation was present only under wave type A ultrasound irradiation. Under the two controlled wave types, the increase in Ca(2+) in L929 fibroblasts was observed with fluorescence imaging. Under wave type A ultrasound irradiation, an increase in Ca(2+) was observed; however, no increase in Ca(2+) was observed under wave type B ultrasound irradiation. We conclude that stable cavitation is involved in the increase of Ca(2+) in cells subjected to pulsed ultrasound. Copyright © 2011 Elsevier B.V. All rights reserved.
Tsai, Chia-Lung; Wu, Hsien-Ming; Lin, Chiao-Yun; Lin, Yi-Jun; Chao, Angel; Wang, Tzu-Hao; Hsueh, Swei; Lai, Chyong-Huey; Wang, Hsin-Shih
2013-01-01
Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of estrogen receptor (ER) through genomic and non-genomic mechanisms and are implicated in the development of endometrial cancer. Previous reports have demonstrated that estradiol and tamoxifen induce proliferation of human endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway. Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30 agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines with or without ERα (Ishikawa and RL95-2). Additionally, the GPR30-mediated cell migration was further abolished by administration of either specific RNA interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues with low or without ERα further suggested that estrogen-induced phosphorylation of FAK and cell migration were most likely triggered by GPR30 activation. These results provided new insights for understanding the pathophysiological functions of GPR30 in human endometrial cancers.
Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.
Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo
2016-01-01
Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier.
Multiplane wave imaging increases signal-to-noise ratio in ultrafast ultrasound imaging.
Tiran, Elodie; Deffieux, Thomas; Correia, Mafalda; Maresca, David; Osmanski, Bruno-Felix; Sieu, Lim-Anna; Bergel, Antoine; Cohen, Ivan; Pernot, Mathieu; Tanter, Mickael
2015-11-07
Ultrafast imaging using plane or diverging waves has recently enabled new ultrasound imaging modes with improved sensitivity and very high frame rates. Some of these new imaging modalities include shear wave elastography, ultrafast Doppler, ultrafast contrast-enhanced imaging and functional ultrasound imaging. Even though ultrafast imaging already encounters clinical success, increasing even more its penetration depth and signal-to-noise ratio for dedicated applications would be valuable. Ultrafast imaging relies on the coherent compounding of backscattered echoes resulting from successive tilted plane waves emissions; this produces high-resolution ultrasound images with a trade-off between final frame rate, contrast and resolution. In this work, we introduce multiplane wave imaging, a new method that strongly improves ultrafast images signal-to-noise ratio by virtually increasing the emission signal amplitude without compromising the frame rate. This method relies on the successive transmissions of multiple plane waves with differently coded amplitudes and emission angles in a single transmit event. Data from each single plane wave of increased amplitude can then be obtained, by recombining the received data of successive events with the proper coefficients. The benefits of multiplane wave for B-mode, shear wave elastography and ultrafast Doppler imaging are experimentally demonstrated. Multiplane wave with 4 plane waves emissions yields a 5.8 ± 0.5 dB increase in signal-to-noise ratio and approximately 10 mm in penetration in a calibrated ultrasound phantom (0.7 d MHz(-1) cm(-1)). In shear wave elastography, the same multiplane wave configuration yields a 2.07 ± 0.05 fold reduction of the particle velocity standard deviation and a two-fold reduction of the shear wave velocity maps standard deviation. In functional ultrasound imaging, the mapping of cerebral blood volume results in a 3 to 6 dB increase of the contrast-to-noise ratio in deep
Sinha, Sonam; Khan, Sajid; Shukla, Samriddhi; Lakra, Amar Deep; Kumar, Sudhir; Das, Gunjan; Maurya, Rakesh; Meeran, Syed Musthapa
2016-08-01
Available breast cancer therapeutic strategies largely target the primary tumor but are ineffective against tumor metastasis and angiogenesis. In our current study, we determined the effect of Cucurbitacin B (CuB), a plant triterpenoid, on the metastatic and angiogenic potential of breast cancer cells. CuB was found to inhibit cellular proliferation and induce apoptosis in breast cancer cells in a time- and dose-dependent manner. Further, CuB-treatment significantly inhibited the migratory and invasive potential of highly metastatic breast cancer MDA-MB-231 and 4T1 cells at sub-IC50 concentrations, where no significant apoptosis was observed. CuB was also found to inhibit migratory, invasive and tube-forming capacities of HUVECs in vitro. In addition, inhibition of pre-existing vasculature in chick embryo chorioallantoic membrane ex vivo further supports the anti-angiogenic effect of CuB. CuB-mediated anti-metastatic and anti-angiogenic effects were associated with the downregulation of VEGF/FAK/MMP-9 signaling, which has been validated by using FAK-inhibitor (FI-14). CuB-treatment resulted in a significant inhibition of VEGF-induced phosphorylation of FAK and MMP-9 expressions similar to the action of FI-14. CuB was also found to decrease the micro-vessel density as evidenced by the decreased expression of CD31, a marker for neovasculature. Further, CuB-treatment inhibited tumor growth, lung metastasis and angiogenesis in a highly metastatic 4T1-syngeneic mouse mammary cancer. Collectively, our findings suggest that CuB inhibited breast cancer metastasis and angiogenesis, at least in part, through the downregulation of VEGF/FAK/MMP-9 signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com
Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs andmore » reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.« less
Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh; Nirujogi, Raja Sekhar; Kim, Min-Sik; Manda, Srikanth S.; Stearns, Vered; Gabrielson, Edward; Sukumar, Saraswati; Pandey, Akhilesh
2015-01-01
Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers. PMID:26330541
Chikara, Shireen; Lindsey, Kaitlin; Borowicz, Pawel; Christofidou-Solomidou, Melpo; Reindl, Katie M
2017-01-09
Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined. We hypothesized that EL could inhibit lung cancer cell motility by affecting the FAK-Src signaling pathway. Non-toxic concentrations of EL were identified for A549 and H460 human lung cancer cells by conducting 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Dephenyltetrazolium Bromide (MTT) assays. The anti-migratory and anti-invasive potential of EL for lung cancer cell lines was determined by scratch wound healing and Matrigel® invasion assays. Changes in filamentous actin (F-actin) fiber density and length in EL-treated cells were determined using phalloidin-conjugated rhodamine dye and fluorescent microscopy. Vinculin expression in focal adhesions upon EL treatment was determined by immunocytochemistry. Gene and protein expression levels of FAK-Src signaling molecules in EL-treated lung cancer cells were determined using PCR arrays, qRT-PCR, and western blotting. Non-toxic concentrations of EL inhibited lung cancer cell migration and invasion in a concentration- and time-dependent manner. EL treatment reduced the density and number of F-actin fibers in lung cancer cell lines, and reduced the number and size of focal adhesions. EL decreased phosphorylation of FAK and its downstream targets, Src, paxillin, and decreased mRNA expression of cell motility-related genes, RhoA, Rac1, and Cdc42 in lung cancer cells. Our data suggest that EL suppresses lung cancer cell motility and invasion by
Modeling ultrasound propagation through material of increasing geometrical complexity.
Odabaee, Maryam; Odabaee, Mostafa; Pelekanos, Matthew; Leinenga, Gerhard; Götz, Jürgen
2018-06-01
Ultrasound is increasingly being recognized as a neuromodulatory and therapeutic tool, inducing a broad range of bio-effects in the tissue of experimental animals and humans. To achieve these effects in a predictable manner in the human brain, the thick cancellous skull presents a problem, causing attenuation. In order to overcome this challenge, as a first step, the acoustic properties of a set of simple bone-modeling resin samples that displayed an increasing geometrical complexity (increasing step sizes) were analyzed. Using two Non-Destructive Testing (NDT) transducers, we found that Wiener deconvolution predicted the Ultrasound Acoustic Response (UAR) and attenuation caused by the samples. However, whereas the UAR of samples with step sizes larger than the wavelength could be accurately estimated, the prediction was not accurate when the sample had a smaller step size. Furthermore, a Finite Element Analysis (FEA) performed in ANSYS determined that the scattering and refraction of sound waves was significantly higher in complex samples with smaller step sizes compared to simple samples with a larger step size. Together, this reveals an interaction of frequency and geometrical complexity in predicting the UAR and attenuation. These findings could in future be applied to poro-visco-elastic materials that better model the human skull. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Ichihara, Eiki; Westover, David; Meador, Catherine B; Yan, Yingjun; Bauer, Joshua A; Lu, Pengcheng; Ye, Fei; Kulick, Amanda; de Stanchina, Elisa; McEwen, Robert; Ladanyi, Marc; Cross, Darren; Pao, William; Lovly, Christine M
2017-06-01
Mutant-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR -mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first- and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR -mutant lung cancer. Despite promising results, therapeutic efficacy is limited by the development of acquired resistance. Here we report that Src family kinases (SFK) and focal adhesion kinase (FAK) sustain AKT and MAPK pathway signaling under continuous EGFR inhibition in osimertinib-sensitive cells. Inhibiting either the MAPK pathway or the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition exhibited the most potent effects on growth inhibition, induction of apoptosis, and delay of acquired resistance. SFK family member YES1 was amplified in osimertinib-resistant EGFR -mutant tumor cells, the effects of which were overcome by combined treatment with osimertinib and SFK inhibitors. In conclusion, our data suggest that the concomitant inhibition of both SFK/FAK and EGFR may be a promising therapeutic strategy for EGFR -mutant lung cancer. Cancer Res; 77(11); 2990-3000. ©2017 AACR . ©2017 American Association for Cancer Research.
Zhan, Cheng; Le-Meng, Zhang; Liu, Hongchun; Cai, Yu; Tu, Chuantao; Li, Xi; Zou, Yanting; Zhang, Shuncai
2017-01-01
Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy. PMID:28186967
Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery
Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.
2013-01-01
The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta®, Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload. PMID:23781287
Lung surfactant microbubbles increase lipophilic drug payload for ultrasound-targeted delivery.
Sirsi, Shashank R; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y; Mountford, Paul A; Borden, Mark A
2013-01-01
The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta(®), Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload.
Zheng, Yanhua; Yang, Weiwei; Xia, Yan; Hawke, David; Liu, David X.; Lu, Zhimin
2011-01-01
Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion and migration. However, the mechanism by which PTP-PEST is regulated in response to oncogenic signaling to dephosphorylate its substrates remains unclear. Here, we demonstrate that activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells. These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression. PMID:21876001
Point-of-care ultrasound education: the increasing role of simulation and multimedia resources.
Lewiss, Resa E; Hoffmann, Beatrice; Beaulieu, Yanick; Phelan, Mary Beth
2014-01-01
This article reviews the current technology, literature, teaching models, and methods associated with simulation-based point-of-care ultrasound training. Patient simulation appears particularly well suited for learning point-of-care ultrasound, which is a required core competency for emergency medicine and other specialties. Work hour limitations have reduced the opportunities for clinical practice, and simulation enables practicing a skill multiple times before it may be used on patients. Ultrasound simulators can be categorized into 2 groups: low and high fidelity. Low-fidelity simulators are usually static simulators, meaning that they have nonchanging anatomic examples for sonographic practice. Advantages are that the model may be reused over time, and some simulators can be homemade. High-fidelity simulators are usually high-tech and frequently consist of many computer-generated cases of virtual sonographic anatomy that can be scanned with a mock probe. This type of equipment is produced commercially and is more expensive. High-fidelity simulators provide students with an active and safe learning environment and make a reproducible standardized assessment of many different ultrasound cases possible. The advantages and disadvantages of using low- versus high-fidelity simulators are reviewed. An additional concept used in simulation-based ultrasound training is blended learning. Blended learning may include face-to-face or online learning often in combination with a learning management system. Increasingly, with simulation and Web-based learning technologies, tools are now available to medical educators for the standardization of both ultrasound skills training and competency assessment.
Horder, M M; Barnett, S B; Vella, G J; Edwards, M J; Wood, A K
1998-11-01
Temperature increase was measured at various depths in the brain of living fetal guinea pigs during in utero exposure to unscanned pulsed ultrasound at ISPTA 2.8 W/cm2. Mean temperature increases of 4.9 degrees C close to parietal bone and 1.2 degrees C in the midbrain were recorded after 2-min exposures. When exposures were repeated on the same sites in each fetus after death, the corresponding mean temperature increases were 4.9 degrees C and 1.3 degrees C, respectively. Cerebral blood perfusion had little cooling effect on ultrasound-induced heating in the guinea pig fetus of 57-61 days gestational age.
Wan, Hin-Ting; Mruk, Dolores D.; Wong, Chris K. C.
2014-01-01
Environmental toxicants such as perfluorooctanesulfonate (PFOS) have been implicated in male reproductive dysfunction, including reduced sperm count and semen quality, in humans. However, the underlying mechanism(s) remains unknown. Herein PFOS at 10–20 μM (∼5–10 μg/mL) was found to be more potent than bisphenol A (100 μM) in perturbing the blood-testis barrier (BTB) function by disrupting the Sertoli cell tight junction-permeability barrier without detectable cytotoxicity. We also delineated the underlying molecular mechanism by which PFOS perturbed Sertoli cell BTB function using an in vitro model that mimics the BTB in vivo. First, PFOS perturbed F-actin organization in Sertoli cells, causing truncation of actin filaments at the BTB. Thus, the actin-based cytoskeleton was no longer capable of supporting the distribution and/or localization of actin-regulatory and adhesion proteins at the cell-cell interface necessary to maintain BTB integrity. Second, PFOS was found to perturb inter-Sertoli cell gap junction (GJ) communication based on a dye-transfer assay by down-regulating the expression of connexin-43, a GJ integral membrane protein. Third, phosphorylated focal adhesion kinase (FAK)-Tyr407 was found to protect the BTB from the destructive effects of PFOS as shown in a study via an overexpression of an FAK Y407E phosphomimetic mutant. Also, transfection of Sertoli cells with an FAK-specific microRNA, miR-135b, to knock down the expression of phosphorylated FAK-Tyr407 was found to worsen PFOS-mediated Sertoli cell tight junction disruption. In summary, PFOS-induced BTB disruption is mediated by down-regulating phosphorylated FAK-Tyr407 and connexin-43, which in turn perturbed F-actin organization and GJ-based intercellular communication, leading to mislocalization of actin-regulatory and adhesion proteins at the BTB. PMID:24169556
Singkhorn, Sawana; Tantisira, Mayuree H; Tanasawet, Supita; Hutamekalin, Pilaiwanwadee; Wongtawatchai, Tulaporn; Sukketsiri, Wanida
2018-03-13
Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay. Formation of filopodia, a key protein in cell migration as well as signaling pathways possibly involved were subsequently assessed. It was found that HaCaT cell migration was significantly enhanced by ECa 233 in a concentration- and time-dependent manner. The filopodia formations were accordingly increased in exposure to ECa 233 at concentrations of 0.1-100 μg/ml. Furthermore, ECa 233 was found to significantly upregulate the expression of Rac1 and RhoA and to induce phosphorylation of FAK and Akt as well as ERK and p38 MAPK. Taken all together, it is suggestive that ECa 233 induces cell migration and subsequently promotes wound healing activity, through the activation of FAK, Akt, and MAPK signaling pathways thereby supporting the role of ECa 233 to be further developed for the clinical treatment of wound. Copyright © 2018 John Wiley & Sons, Ltd.
Prolactin-Induced Tyrosine Phosphorylation, Activation and Receptor
Association of Focal Adhesion Kinase (FAK) in Mammary Epithelial Cells.
Suzanne E. Fenton1 and Lewis G. Sheffield2. 1U.S. Environmental Protection
Agency, MD-72, Research Triangle Park, NC 27711, and
Fang, Yu; Wang, Dawei; Xu, Xingyu; Liu, Jianping; Wu, Aiqin; Li, Xiang; Xue, Qianqian; Wang, Huan; Wang, Hang; Zhang, Huabei
2017-02-15
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N 2 -(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N 4 -(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC 50 in the range of 91.4-425.7 nM, and among which the result of the [ 19 F]2 was relatively good and had a modest IC 50 of 91.4 nM. The [ 19 F]2 was also profiled in vitro against some other kinds of cancer-related kinases (including two kinds of non-receptor tyrosine kinase: PYK2 and JAK2, and three kinds of receptor tyrosine kinase: IGF-1R, EGFR and PDGFRβ). It displayed 25.2 folds selectivity against PYK2, 35.1 folds selectivity against EGFR, and more than 100 folds selectivity against IGF-1R, JAK2 and PDGFRβ. For the biodistribution in S180 bearing mice, the corresponding [ 18 F]2 were also relatively good, with modest tumor uptake of 5.47 ± 0.19 and 5.80 ± 0.06 %ID/g at 15 and 30 min post-injection, respectively. Furthermore, its tumor/muscle, tumor/bone and tumor/blood ratio at 15 min post-injection were 3.16, 2.53 and 4.52, respectively. And its tumor/muscle, tumor/bone and tumor/blood ratio at 30 min post-injection were 3.14, 2.76 and 4.43, respectively. In addition, coronal micro-PET/CT images of a mouse bearing S180 tumor clearly confirmed that [ 18 F]2 could be accumulated in tumor, especially at 30 min post-injection. Besides, for the [ 18 F]2, both the biodistribution data and the micro-PET/CT imaging study showed significantly reduced uptake of the radiotracer in the tumor tissue at 30 min post-injection in mice that received PF-562,271 (one of the reported best selective FAK inhibitor which was developed by Pfitzer Inc
Skin temperature increase mediated by wearable, long duration, low-intensity therapeutic ultrasound
NASA Astrophysics Data System (ADS)
Langer, Matthew D.; Huang, Wenyi; Ghanem, Angi; Guo, Yuan; Lewis, George K.
2017-03-01
One of the safety concerns with the delivery of therapeutic ultrasound is overheating of the transducer-skin interface due to poor or improper coupling. The objective of this research was to define a model that could be used to calculate the heating in the skin as a result of a novel, wearable long-duration ultrasound device. This model was used to determine that the maximum heating in the skin remained below the minimum threshold necessary to cause thermal injury over multiple hours of use. In addition to this model data, a human clinical study used wire thermocouples on the skin surface to measure heating characteristics during treatment with the sustained ultrasound system. Parametric analysis of the model determined that the maximum temperature increase is at the surface of the skin ranged from 40-41.8° C when perfusion was taken into account. The clinical data agreed well with the model predictions. The average steady state temperature observed across all 44 subjects was 40°C. The maximum temperature observed was less than 44° C, which is clinically safe for over 5 hours of human skin contact. The resultant clinical temperature data paired well with the model data suggesting the model can be used for future transducer and ultrasound system design simulation. As a result, the device was validated for thermal safety for typical users and use conditions.
Cantisani, Vito; Maceroni, Piero; D'Andrea, Vito; Patrizi, Gregorio; Di Segni, Mattia; De Vito, Corrado; Grazhdani, Hektor; Isidori, Andrea M; Giannetta, Elisa; Redler, Adriano; Frattaroli, Fabrizio; Giacomelli, Laura; Di Rocco, Giorgio; Catalano, Carlo; D'Ambrosio, Ferdinando
2016-05-01
To assess whether ultrasound elastography (USE) with strain ratio increases diagnostic accuracy of Doppler ultrasound in further characterisation of cytologically Thy3 thyroid nodules. In two different university diagnostic centres, 315 patients with indeterminate cytology (Thy3) in thyroid nodules aspirates were prospectively evaluated with Doppler ultrasound and strain ratio USE before surgery. Ultrasonographic features were analysed separately and together as ultrasound score, to assess sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves to identify optimal cut-off value of the strain ratio were also provided. Diagnosis on a surgical specimen was considered the standard of reference. Higher strain ratio values were found in malignant nodules, with an optimum strain ratio cut-off of 2.09 at ROC analysis. USE with strain ratio showed 90.6% sensitivity, 93% specificity, 82.8% PPV, 96.4% NPV, while US score yielded a sensitivity of 52.9%, specificity of 84.3%, PPV 55.6% and NPV 82.9%. The diagnostic gain with strain ratio was statistically significant as proved by ROC areas, which was 0.9182 for strain ratio and 0.6864 for US score. USE with strain ratio should be considered a useful additional tool to colour-Doppler US, since it improves characterisation of thyroid nodules with indeterminate cytology. • Strain ratio measurements improve differentiation of thyroid nodules with indeterminate cytology • Elastography with strain ratio is more reliable than ultrasound features and ultrasound score • Strain ratio may help to better select patients with Thy 3 nodules candidate for surgery.
Does use of a PACS increase the number of images per study? A case study in ultrasound.
Horii, Steven; Nisenbaum, Harvey; Farn, James; Coleman, Beverly; Rowling, Susan; Langer, Jill; Jacobs, Jill; Arger, Peter; Pinheiro, Lisa; Klein, Wendy; Reber, Michele; Iyoob, Christopher
2002-03-01
The purpose of this study was to determine if the use of a picture archiving and communications system (PACS) in ultrasonography increased the number of images acquired per examination. The hypothesis that such an increase does occur was based on anecdotal information; this study sought to test the hypothesis. A random sample of all ultrasound examination types was drawn from the period 1998 through 1999. The ultrasound PACS in use (ACCESS; Kodak Health Information Systems, Dallas, TX) records the number of grayscale and color images saved as part of each study. Each examination in the sample was checked in the ultrasound PACS database,.and the number of grayscale and color images was recorded. The comparison film-based sample was drawn from the period 1994 through 1995. The number of examinations of each type selected was based on the overall statistics of the section; that is, the sample was designed to represent the approximate frequency with which the various examination types are done. For film-based image counts, the jackets were retrieved, and the number of grayscale and color images were counted. The number of images obtained per examination (for most examinations) in ultrasound increased with PACS use. This was more evident with some examination types (eg, pelvis). This result, however, has to be examined for possible systematic biases because ultrasound practice has changed over the time since the authors stopped using film routinely. The use of PACS in ultrasonography was not associated with an increase in the number of images per examination based solely on the use of PACS, with the exception of neonatal head studies. Increases in the number of images per study was otherwise associated with examinations for which changes in protocols resulted in the increased image counts.
Mahankali, Madhu; Henkels, Karen M.; Speranza, Francis; Gomez-Cambronero, Julian
2015-01-01
ABSTRACT Timely activation of Aurora kinase A (AURA, also known as AURKA) is vital for centrosome formation and the progression of mitosis. Nonetheless, it is still unclear if and when other cellular functions are activated by AURA. We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement. An additional and new way by which AURA is regulated, is by phospholipase D2 (PLD2), which causes AURA activation. In addition, AURA phosphorylates PLD, so both proteins engage in a positive reinforcement loop. AURA and PLD2 form a protein–protein complex and colocalize to cytoplasmic regions in cells. The reason why PLD activates AURA is because of the production of phosphatidic acid by the lipase, which binds directly to AURA, with the region E171–E211 projected to be a phosphatidic-acid-binding pocket. Furthermore, this direct interaction with phosphatidic acid enhances tubulin polymerization and cooperates synergistically with AURA, FAK and Src in yielding a fully effectual cellular migration. Thus, Src and FAK, and PLD and phosphatidic acid are new upstream regulators of AURA that mediate its role in the non-mitotic cellular function of cell migration. PMID:25501815
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xi, Wei-Hong; Yang, Li-Yun; Cao, Zhong-Yi, E-mail: m18070383032@163.com
Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and the 5 years survival rate of the patients is about 60% in the USA, due to acquired chemotherapeutic resistance and metastasis of the disease. In this study, we found that tivantinib, a selective MET inhibitor, suppresses OCSS cell proliferation and colony formation, however, anti-tumor activities induced by tivantinib are independent of the inhibition of MET signaling pathway. In addition, tivantinib cause G2/M cell cycle arrest and caspases-dependent apoptosis in OSCC cell lines. We also found that tivantinib dose-dependently suppressed the activation and expression of FAK. Inmore » all, these data suggested that tivantinib may be developed as a chemotherapeutic agent to effectively treat certain cancers including OSCC. - Highlights: • Tivantinib suppresses OSCC cell growth independent of the inhibition of HGF/MET signaling pathway. • Tivantinib blocks cell cycle and induces caspases-mediated apoptosis. • Tivantinib elicits its anti-tumor activity with the inhibition of FAK signaling pathway.« less
Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway
Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y.; Iida, Machiko; Suzuki, Tamio; Kato, Masashi
2015-01-01
Deltex-3-like (DTX3L), an E3 ligase, is a member of the Deltex (DTX) family and is also called B-lymphoma and BAL-associated protein (BBAP). Previously, we established RFP/RET-transgenic mice, in which systemic hyperpigmented skin, benign melanocytic tumor(s) and melanoma(s) develop stepwise. Here we showed that levels of Dtx3l/DTX3L in spontaneous melanoma in RFP/RET-transgenic mice and human melanoma cell lines were significantly higher than those in benign melanocytic cells and primarily cultured normal human epithelial melanocytes, respectively. Immunohistochemical analysis of human tissues showed that more than 80% of the melanomas highly expressed DTX3L. Activity of FAK/PI3K/AKT signaling, but not that of MEK/ERK signaling, was decreased in Dtx3l/DTX3L-depleted murine and human melanoma cells. In summary, we demonstrated not only increased DTX3L level in melanoma cells but also DTX3L-mediated regulation of invasion and metastasis in melanoma through FAK/PI3K/AKT but not MEK/ERK signaling. Our analysis in human BRAFV600E inhibitor-resistant melanoma cells showed about 80% decreased invasion in the DTX3L-depleted cells compared to that in the DTX3L-intact cells. Thus, DTX3L is clinically a potential therapeutic target as well as a potential biomarker for melanoma. PMID:26033450
Zhao, Yawei; Cui, Lianzhi; Pan, Yue; Shao, Dan; Zheng, Xiao; Zhang, Fan; Zhang, Hansi; He, Kan; Chen, Li
2017-12-01
Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE 2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE 2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA 2 -AA-COX-2-PGE 2 pathway by inhibiting the expression of iPLA 2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE 2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. © 2017 John Wiley & Sons Ltd.
Wu, Ziqi; Kumon, Ronald E; Laughner, Jacob I; Efimov, Igor R; Deng, Cheri X
2015-02-01
To gain better understanding of the detailed mechanisms of high-intensity focused ultrasound (HIFU) ablation for cardiac arrhythmias, we investigated how the cellular electrophysiological (EP) changes were correlated with temperature increases and thermal dose (cumulative equivalent minutes [CEM43]) during HIFU application using Langendorff-perfused rabbit hearts. Employing voltage-sensitive dye di-4-ANEPPS, we measured the EP and temperature during HIFU using simultaneous optical mapping and infrared imaging. Both action potential amplitude (APA) and action potential duration at 50% repolarization (APD50) decreased with temperature increases, and APD50 was more thermally sensitive than APA. EP and tissue changes were irreversible when HIFU-induced temperature increased above 52.3 ± 1.4°C and log10(CEM43) above 2.16 ± 0.51 (n = 5), but were reversible when temperature was below 50.1 ± 0.8°C and log10(CEM43) below -0.9 ± 0.3 (n = 9). EP and temperature/thermal dose changes were spatially correlated with HIFU-induced tissue necrosis surrounded by a transition zone. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Chaturvedi, Lakshmi S.; Marsh, Harold M.
2011-01-01
Repetitive deformation enhances intestinal epithelial migration across tissue fibronectin. We evaluated the contribution of RhoA and its effectors Rho-associated kinase (ROK/ROCK) and mammalian diaphanous formins (mDia1) to deformation-induced intestinal epithelial motility across fibronectin and the responsible focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), p38, and myosin light chain (MLC) signaling. We reduced RhoA, ROCK1, ROCK2, and mDia1 by smart-pool double-stranded short-interfering RNAs (siRNA) and pharmacologically inhibited RhoA, ROCK, and FAK in human Caco-2 intestinal epithelial monolayers on fibronectin-coated membranes subjected to 10% repetitive deformation at 10 cycles/min. Migration was measured by wound closure. Stimulation of migration by deformation was prevented by exoenzyme C3, Y27632, or selective RhoA, ROCK1, and ROCK2 or mDia1 siRNAs. RhoA, ROCK inhibition, or RhoA, ROCK1, ROCK2, mDia1, and FAK reduction by siRNA blocked deformation-induced nuclear ERK phosphorylation without preventing ERK phosphorylation in the cytoplasmic protein fraction. Furthermore, RhoA, ROCK inhibition or RhoA, ROCK1, ROCK2, and mDia1 reduction by siRNA also blocked strain-induced FAK-Tyr925, p38, and MLC phosphorylation. These results suggest that RhoA, ROCK, mDia1, FAK, ERK, p38, and MLC all mediate the stimulation of intestinal epithelial migration by repetitive deformation. This pathway may be an important target for interventions to promote mechanotransduced mucosal healing during inflammation. PMID:21849669
Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Fahad, Mohamed; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M
2018-03-02
Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH + positive cells are clonogenic and highly proliferative; their global gene expression profiling-based molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH + cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH + cell fraction among the SW403, HCT116 and SW620 CRC models. Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or 420 patients for overall (OS) or disease-free (DFS) survival, respectively, obtained from the Cancer Genome Atlas CRC dataset, revealed strong association between elevated expression and poor OS ( p = 0.006) and poor DFS ( p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH + CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC.
Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Fahad, Mohamed; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M.
2018-01-01
Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH+ positive cells are clonogenic and highly proliferative; their global gene expression profiling-based molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH+ cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH+ cell fraction among the SW403, HCT116 and SW620 CRC models. Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or 420 patients for overall (OS) or disease-free (DFS) survival, respectively, obtained from the Cancer Genome Atlas CRC dataset, revealed strong association between elevated expression and poor OS (p = 0.006) and poor DFS (p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH+ CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC. PMID:29568377
2010-01-01
Background The Blood Brain Barrier (BBB) maintains the homeostasis of central nervous system by preventing the free passage of macromolecules from the systemic circulation into the brain. This normal physiological function of the BBB presents a challenge for delivery of therapeutic compounds into the brain. Recent studies have shown that the application of focused ultrasound together with ultrasound contrast agent (microbubbles) temporarily increases the permeability of the BBB. This effect is associated with breakdown of tight junctions, the structures that regulate the paracellular permeability of the endothelial cell layer. The influence of this ultrasound effect on the activation of intracellular signaling proteins is currently not well understood. Therefore, the aim of this study was to investigate the activation of cell survival signaling molecules in response to ultrasound-mediated BBB opening; Methods The BBB was disrupted in two four-spot lines (1-1.5 mm spacing) along the right hemisphere of rat brain with ultrasound beams (0.3 MPa, 120 s, 10 ms bursts, repetition frequency = 1 Hz) in the presence Definity microbubbles. Contrast-enhanced MRI images were acquired to assess the extent of BBB opening upon which the animals were sacrificed and the brains removed and processed for biochemical and immunohistochemical analyses; Results Immunoblotting of sonicated brain lysates resolved by SDS-PAGE demonstrated an increase in phosphorylation of Akt and its downstream signaling molecule, GSK3β, while the phosphorylation of MAPK remained unchanged. The elevated levels of pAkt and pGSK3β are still evident after 24 hours post-sonication, a time point where the integrity of the BBB is known to be re-established. Furthermore, immunofluoresence staining localized this increase in pAkt and pGSK3β levels to neuronal cells flanking the region of the disrupted BBB; Conclusions Our data demonstrates that ultrasound-mediated BBB disruption causes an activation of the Akt
Lin, Su-Hsuan; Shih, Yuan-Wei
2014-06-01
Chalcones (benzylideneacetophenone) are cancer-preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in human gastric adenocarcinoma cell lines: AGS. The results showed that chalcone could inhibit the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, Boyden chamber invasion/migration assay, and wound-healing assay. Molecular data showed that the effect of chalcone in AGS cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) and c-Jun N-terminal kinase 1 and 2 (JNK1/2) signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Next, chalcone-treated AGS cells showed tremendous decrease in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, treating FAK small interfering RNA (FAK siRNA) and specific inhibitor for JNK (SP600125) to AGS cells could reduce the phosphorylation of JNK1/2 and the activity of MMP-2 and MMP-9. Our results revealed that chalcone significantly inhibited the metastatic ability of AGS cells by reducing MMP-2 and MMP-9 expressions concomitantly with a marked reduction on cell invasion and migration through suppressing and JNK signaling pathways. We suggest that chalcone may offer the application in clinical medicine.
Nightingale, Kathryn R; Church, Charles C; Harris, Gerald; Wear, Keith A; Bailey, Michael R; Carson, Paul L; Jiang, Hui; Sandstrom, Kurt L; Szabo, Thomas L; Ziskin, Marvin C
2015-07-01
The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues. © 2015 by the American Institute of
Pulpal temperature increase with high-speed handpiece, Er:YAG laser and ultrasound tips.
Mollica, Fernanda Brandão; Camargo, Fernanda Pelogia; Zamboni, Sandra Costa; Pereira, Sarina Maciel Braga; Teixeira, Symone Cristina; Nogueira, Lafayette
2008-01-01
The aim of this study was to compare intrapulpal temperature increase produced by high-speed handpiece, Er:YAG laser and CVDentus ultrasound tips during cavity preparation. Thirty bovine mandibular incisors with an enamel/dentin thickness of 4 mm at buccal surface had their roots amputated and were allocated to the following groups (n=10): Group I- high-speed handpiece; Group II- noncontact Er:YAG laser (250 mJ/4 Hz); and Group III- CVDentus ultrasouns tips. All devices were used with water cooling. Class V cavities were prepared to a depth of 3.5 mm, measured with a periodontal probe. A type T thermocouple was placed inside the pulp chamber to determine the temperature increase (degrees C), which was recorded by a data acquisition system ADS 2000 IP (Lynx Technology) linked to a notebook computer. Data were analyzed statistically by one-way ANOVA and Tukey's test (p=0.05). The mean temperature rises were: 1.10 degrees C (+/-0.56) for Group I, 0.84 degrees C (+/-0.55) for Group II, and 3.00 degrees C (+/- 1.34) for Group III. There were no statistically significant differences (p>0.05) between Groups I and II, but both of them differed significantly from Group III (p<0.05). In conclusion, the use of Er:YAG laser and high-speed handpiece for cavity preparation resulted in similar temperature increase. Although ultrasound tips generated significantly higher intrapulpal temperature increase, it remained below the critical value of 5.5 degrees C and may be considered safe for use.
Integrated medical school ultrasound: development of an ultrasound vertical curriculum.
Bahner, David P; Adkins, Eric J; Hughes, Daralee; Barrie, Michael; Boulger, Creagh T; Royall, Nelson A
2013-07-02
Physician-performed focused ultrasonography is a rapidly growing field with numerous clinical applications. Focused ultrasound is a clinically useful tool with relevant applications across most specialties. Ultrasound technology has outpaced the education, necessitating an early introduction to the technology within the medical education system. There are many challenges to integrating ultrasound into medical education including identifying appropriately trained faculty, access to adequate resources, and appropriate integration into existing medical education curricula. As focused ultrasonography increasingly penetrates academic and community practices, access to ultrasound equipment and trained faculty is improving. However, there has remained the major challenge of determining at which level is integrating ultrasound training within the medical training paradigm most appropriate. The Ohio State University College of Medicine has developed a novel vertical curriculum for focused ultrasonography which is concordant with the 4-year medical school curriculum. Given current evidenced-based practices, a curriculum was developed which provides medical students an exposure in focused ultrasonography. The curriculum utilizes focused ultrasonography as a teaching aid for students to gain a more thorough understanding of basic and clinical science within the medical school curriculum. The objectives of the course are to develop student understanding in indications for use, acquisition of images, interpretation of an ultrasound examination, and appropriate decision-making of ultrasound findings. Preliminary data indicate that a vertical ultrasound curriculum is a feasible and effective means of teaching focused ultrasonography. The foreseeable limitations include faculty skill level and training, initial cost of equipment, and incorporating additional information into an already saturated medical school curriculum. Focused ultrasonography is an evolving concept in medicine
Hot topics in biomedical ultrasound: ultrasound therapy and its integration with ultrasonic imaging
NASA Astrophysics Data System (ADS)
Everbach, E. Carr
2005-09-01
Since the development of biomedical ultrasound imaging from sonar after WWII, there has been a clear divide between ultrasonic imaging and ultrasound therapy. While imaging techniques are designed to cause as little change as possible in the tissues through which ultrasound propagates, ultrasound therapy typically relies upon heating or acoustic cavitation to produce a desirable therapeutic effect. Concerns over the increasingly high acoustic outputs of diagnostic ultrasound scanners prompted the adoption of the Mechanical Index (MI) and Thermal Index (TI) in the early 1990s. Therapeutic applications of ultrasound, meanwhile, have evolved from deep tissue heating in sports medicine to include targeted drug delivery, tumor and plaque ablation, cauterization via high intensity focused ultrasound (HIFU), and accelerated dissolution of blood clots. The integration of ultrasonic imaging and therapy in one device is just beginning, but the promise of improved patient outcomes is balanced by regulatory and practical impediments.
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.
Shi, Shuang; Zhong, Dong; Xiao, Yao; Wang, Bing; Wang, Wentao; Zhang, Fu'an; Huang, Haoyang
2017-06-20
Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.
Oyanadel, Claudia; Holmes, Christopher; Pardo, Evelyn; Retamal, Claudio; Shaughnessy, Ronan; Smith, Patricio; Cortés, Priscilla; Bravo-Zehnder, Marcela; Metz, Claudia; Feuerhake, Teo; Romero, Diego; Roa, Juan Carlos; Montecinos, Viviana; Soza, Andrea; González, Alfonso
2018-01-01
Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial–mesenchymal-transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective β1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin–Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by α5β1integrin binding. Under subconfluent conditions, Gal-8–overexpressing MDCK cells (MDCK-Gal-8H) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased β-catenin activity. Changes related to migration/invasion included higher expression of α5β1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8–stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and β1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8H cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties. PMID:29298841
Pregnancy sonogram; Obstetric ultrasonography; Obstetric sonogram; Ultrasound - pregnancy; IUGR - ultrasound; Intrauterine growth - ultrasound; Polyhydramnios - ultrasound; Oligohydramnios - ultrasound; Placenta previa - ultrasound; Multiple pregnancy - ultrasound; ...
Ultrasound enhances retrovirus-mediated gene transfer.
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
Wang, Chao-Qun; Huang, Yu-Wen; Wang, Shih-Wei; Huang, Yuan-Li; Tsai, Chun-Hao; Zhao, Yong-Ming; Huang, Bi-Fei; Xu, Guo-Hong; Fong, Yi-Chin; Tang, Chih-Hsin
2017-01-28
Chondrosarcoma is the second most common primary malignancy of bone after myeloma and osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). The expression of VEGF-A has been recognized as a prognostic marker in angiogenesis. Amphiregulin (AR), an epidermal growth factor receptor ligand, promotes tumor proliferation, metastasis and angiogenesis. However, the role of AR in VEGF-A expression and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that AR promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, AR-enhanced VEGF-A expression and angiogenesis involved the FAK, c-Src and PKCδ signaling pathways, while miR-206 expression was negatively mediated by AR via the FAK, c-Src and PKCδ pathways. Our results illustrate the clinical significance between AR, VEGF-A and miR-206, as well as tumor stage, in human chondrosarcoma. AR may represent a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ultrasound-guided synovial biopsy
Sitt, Jacqueline C M; Wong, Priscilla
2016-01-01
Ultrasound-guided needle biopsy of synovium is an increasingly performed procedure with a high diagnostic yield. In this review, we discuss the normal synovium, as well as the indications, technique, tissue handling and clinical applications of ultrasound-guided synovial biopsy. PMID:26581578
Endovaginal ultrasound; Ultrasound - transvaginal; Fibroids - transvaginal ultrasound; Vaginal bleeding - transvaginal ultrasound; Uterine bleeding - transvaginal ultrasound; Menstrual bleeding - transvaginal ultrasound; ...
... community Home > Pregnancy > Prenatal care > Ultrasound during pregnancy Ultrasound during pregnancy E-mail to a friend Please ... you. What are some reasons for having an ultrasound? Your provider uses ultrasound to do several things, ...
Nightingale, Kathryn R.; Church, Charles C.; Harris, Gerald; Wear, Keith A.; Bailey, Michael R.; Carson, Paul L.; Jiang, Hui; Sandstrom, Kurt L.; Szabo, Thomas L.; Ziskin, Marvin C.
2016-01-01
The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term “conditionally” is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues. PMID:26112617
Quantitative Ultrasound Backscatter for Pulsed Cavitational Ultrasound Therapy—Histotripsy
Wang, Tzu-Yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L.; Fowlkes, J. Brian; Rothman, Edward D.; Roberts, William W.; Cain, Charles A.
2011-01-01
Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs. This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology. Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated. PMID:19750596
Quantitative ultrasound backscatter for pulsed cavitational ultrasound therapy- histotripsy.
Wang, Tzu-yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L; Fowlkes, J Brian; Rothman, Edward D; Roberts, William W; Cain, Charles A
2009-05-01
Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs.This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology.Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated.
Impact of ultrasound video transfer on the practice of ultrasound
NASA Astrophysics Data System (ADS)
Duerinckx, Andre J.; Hayrapetian, Alek S.; Grant, Edward G.; Valentino, Daniel J.; Rahbar, Darius; Kiszonas, Mike; Franco, Ricky; Melany, Michelle; Narin, Sherelle L.; Ragavendra, Nagesh
1996-05-01
Sonography can be highly dependent on real-time imaging and as such is highly physician intensive. Such situations arise mostly during complicated ultrasound radiology studies or echocardiology examinations. Under those circumstances it would be of benefit to transmit real-time images beyond the immediate area of the ultrasound laboratory when a physician is not on location. We undertook this study to determine if both static and dynamic image transfer to remote locations might be accomplished using an ultrafast ATM network and PACS. Image management of the local image files was performed by a commercial PACS from AGFA corporation. The local network was Ethernet based, and the global network was based on Asynchronous Transfer Mode (ATM, rates up to 100 Mbits/sec). Real-time image transfer involved two teaching hospitals, one of which had 2 separate ultrasound facilities. Radiologists consulted with technologists via telephone while the examinations were being performed. The applications of ATM network providing real time video for ultrasound imaging in a clinical environment and its potential impact on health delivery and clinical teaching. This technology increased technologist and physician productivity due to the elimination of commute time for physicians and waiting time for technologists and patients. Physician confidence in diagnosis increased compared to reviewing static images alone. This system provided instant access for radiologists to real-time scans from remote sites. Image quality and frame rate were equivalent to the original. The system increased productivity by allowing physicians to monitor studies at multiple sites simultaneously.
Vascular ultrasound; Peripheral vascular ultrasound ... A duplex ultrasound combines: Traditional ultrasound: This uses sound waves that bounce off blood vessels to create pictures. Doppler ultrasound: This ...
Research interface on a programmable ultrasound scanner.
Shamdasani, Vijay; Bae, Unmin; Sikdar, Siddhartha; Yoo, Yang Mo; Karadayi, Kerem; Managuli, Ravi; Kim, Yongmin
2008-07-01
Commercial ultrasound machines in the past did not provide the ultrasound researchers access to raw ultrasound data. Lack of this ability has impeded evaluation and clinical testing of novel ultrasound algorithms and applications. Recently, we developed a flexible ultrasound back-end where all the processing for the conventional ultrasound modes, such as B, M, color flow and spectral Doppler, was performed in software. The back-end has been incorporated into a commercial ultrasound machine, the Hitachi HiVision 5500. The goal of this work is to develop an ultrasound research interface on the back-end for acquiring raw ultrasound data from the machine. The research interface has been designed as a software module on the ultrasound back-end. To increase the amount of raw ultrasound data that can be spooled in the limited memory available on the back-end, we have developed a method that can losslessly compress the ultrasound data in real time. The raw ultrasound data could be obtained in any conventional ultrasound mode, including duplex and triplex modes. Furthermore, use of the research interface does not decrease the frame rate or otherwise affect the clinical usability of the machine. The lossless compression of the ultrasound data in real time can increase the amount of data spooled by approximately 2.3 times, thus allowing more than 6s of raw ultrasound data to be acquired in all the modes. The interface has been used not only for early testing of new ideas with in vitro data from phantoms, but also for acquiring in vivo data for fine-tuning ultrasound applications and conducting clinical studies. We present several examples of how newer ultrasound applications, such as elastography, vibration imaging and 3D imaging, have benefited from this research interface. Since the research interface is entirely implemented in software, it can be deployed on existing HiVision 5500 ultrasound machines and may be easily upgraded in the future. The developed research
Su, Linlin; Mruk, Dolores D.; Lui, Wing-Yee; Lee, Will M.; Cheng, C. Yan
2011-01-01
The blood–testis barrier (BTB), one of the tightest blood–tissue barriers in the mammalian body, creates an immune-privileged site for postmeiotic spermatid development to avoid the production of antibodies against spermatid-specific antigens, many of which express transiently during spermiogenesis and spermiation. However, the BTB undergoes extensive restructuring at stage VIII of the epithelial cycle to facilitate the transit of preleptotene spermatocytes and to prepare for meiosis. This action thus prompted us to investigate whether this stage can be a physiological window for the delivery of therapeutic and/or contraceptive drugs across the BTB to exert their effects at the immune-privileged site. Herein, we report findings that P-glycoprotein, an ATP-dependent efflux drug transporter and an integrated component of the occludin/zonula occludens 1 (ZO-1) adhesion complex at the BTB, structurally interacted with focal adhesion kinase (FAK), creating the occludin/ZO-1/FAK/P-glycoprotein regulatory complex. Interestingly, a knockdown of P-glycoprotein by RNAi was found to impede Sertoli cell BTB function, making the tight junction (TJ) barrier “leaky.” This effect was mediated by changes in the protein phosphorylation status of occludin via the action of FAK, thereby affecting the endocytic vesicle-mediated protein trafficking events that destabilized the TJ barrier. However, the silencing of P-glycoprotein, although capable of impeding drug transport across the BTB and TJ permeability barrier function, was not able to induce the BTB to be “freely” permeable to adjudin. These findings indicate that P-glycoprotein is involved in BTB restructuring during spermatogenesis but that P-glycoprotein–mediated restructuring does not “open up” the BTB to make it freely permeable to drugs. PMID:22106313
Saranya, Jayaram; Shilpa, Ganesan; Raghu, Kozhiparambil G.; Priya, Sulochana
2017-01-01
Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner. The detached cells failed to re-adhere and grew even to culture plates coated with different matrix proteins. DNA fragmentation, membrane integrity studies, annexin V staining, caspase 9 activation and upregulation of Bax/Bad confirmed that the detached cells underwent apoptosis. Upregulation of matrix metalloproteinase 9 (MMP-9) caused a decrease in fibronectin (FN) production which facilitated the cells to detach by blocking the FN mediated downstream signaling. On treatment with MLL, we have observed downregulation of integrin expression, decreased phosphorylation of focal adhesion kinase (FAK), loss in FAK-integrin interaction and active Ras. MLL treatment downregulated the levels of phosphorylated Akt and PI3K. Also, we have studied the effect of MLL on two stress activated protein kinases p38 MAPK and JNK. p38 MAPK activation was found to be elevated, but there was no change in the level of JNK. Thus our study substantiated the possible antimetastatic effect of MLL by inducing anoikis in MCF-7 cells by activation of caspase 9 and proapoptotic Bax/Bad by blockage of FN mediated integrin/FAK signaling and partly by activation of p38 MAPK. PMID:28223935
Effect of modulated ultrasound parameters on ultrasound-induced thrombolysis.
Soltani, Azita; Volz, Kim R; Hansmann, Doulas R
2008-12-07
The potential of ultrasound to enhance enzyme-mediated thrombolysis by application of constant operating parameters (COP) has been widely demonstrated. In this study, the effect of ultrasound with modulated operating parameters (MOP) on enzyme-mediated thrombolysis was investigated. The MOP protocol was applied to an in vitro model of thrombolysis. The results were compared to a COP with the equivalent soft tissue thermal index (TIS) over the duration of ultrasound exposure of 30 min (p < 0.14). To explore potential differences in the mechanism responsible for ultrasound-induced thrombolysis, a perfusion model was used to measure changes in average fibrin pore size of clot before, after and during exposure to MOP and COP protocols and cavitational activity was monitored in real time for both protocols using a passive cavitation detection system. The relative lysis enhancement by each COP and MOP protocol compared to alteplase alone yielded values of 33.69 +/- 12.09% and 63.89 +/- 15.02% in a thrombolysis model, respectively (p < 0.007). Both COP and MOP protocols caused an equivalent significant increase in average clot pore size of 2.09 x 10(-2) +/- 0.01 microm and 1.99 x 10(-2) +/- 0.004 microm, respectively (p < 0.74). No signatures of inertial or stable cavitation were observed for either acoustic protocol. In conclusion, due to mechanisms other than cavitation, application of ultrasound with modulated operating parameters has the potential to significantly enhance the relative lysis enhancement compared to application of ultrasound with constant operating parameters.
Choi, Yun-Hee; Yang, Dong Joo; Kulkarni, Atul; Moh, Sang Hyun; Kim, Ki Woo
2015-01-01
Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also involved in the modulation of skin fibroblasts proliferation. However, the regulatory function of MAAs on wound repair in human skin is not yet clearly elucidated. To investigate the roles of MAAs on the wound healing process in human keratinocytes, three MAAs, Shinorine (SH), Mycosporine-glycine (M-Gly), and Porphyra (P334) were purified from Chlamydomonas hedlyei and Porphyra yezoensis. We found that SH, M-Gly, and P334 have significant effects on the wound healing process in human keratinocytes and these effects were mediated by activation of focal adhesion kinases (FAK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK). These results suggest that MAAs accelerate wound repair by activating the FAK-MAPK signaling pathways. This study also indicates that MAAs can act as a new wound healing agent and further suggests that MAAs might be a novel biomaterial for wound healing therapies. PMID:26703626
Driving delivery vehicles with ultrasound ☆
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
Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Hwang, Eun Hye; Jung, Minji; Moon, Woo Kyung
2016-08-02
The role of microRNA-200 (miR-200) family members in the migration and invasion of breast cancer is controversial. This study investigated the mechanisms by which the miR-200 family members modulated the migratory and invasive abilities of an aggressive triple-negative breast cancer (TNBC) cell line, MDA-MB-231. The miR-200 family (miR-200b/200a/429 and miR-141/200c clusters) and green fluorescence protein (GFP) were transduced into MDA-MB-231 cells using a lentiviral system. Stable cells highly expressing the miR-200 family and GFP were isolated by puromycin selection and fluorescence-activated cell sorting. Gene expression was evaluated using real-time polymerase chain reaction (PCR) and reverse transcriptase-PCR (RT-PCR). The migratory and invasive abilities were assessed using trans-well and wound-healing assays. The secreted cytokines and growth factors in cultured media were quantified using a Bio-Plex200 multiplex array system. Western blot assays and immunofluorescence staining were conducted to investigate miR-200 family-regulated signaling pathways. The entire dataset obtained in this study was statistically evaluated using a one-way ANOVA followed by a t-test. The stable overexpression of the miR-200b/200a/429 or miR-141/200c cluster suppressed cell growth and significantly increased migration and invasion of MDA-MB-231 cells. miR-141/200c overexpression was more effective in decreasing cell growth and promoting migration and invasion of MDA-MB-231 cells than was miR-200b/200a/429 overexpression. In addition, the overexpression of the miR-200b/200a/429 or miR-141/200c cluster led to an increase in the phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT). Chemical inhibitors of FAK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT suppressed the migration and invasion of MDA-MB-231 cells that was enhanced by the overexpression of the miR-200b/200a/429 or miR-141/200c cluster. Compared to the miR-200b/200a/429 cluster
NASA Astrophysics Data System (ADS)
Hughes, Alec; Hynynen, Kullervo
2017-09-01
The use of a phased array of ultrasound transducer elements to sonicate through the skull has opened the way for new treatments and the delivery of therapeutics beyond the blood-brain barrier. The limited steering range of current clinical devices, particularly at higher frequencies, limits the regions of the brain that are considered treatable by ultrasound. A new array design is introduced that allows for high levels of beam steering and increased transmission throughout the brain. These improvements are achieved using concave transducers normal to the outer-skull surface in a patient-specific configuration to target within the skull, so that the far-field of each beam is within the brain. It is shown that by using pulsed ultrasound waves timed to arrive in-phase at the desired target, sufficient levels of acoustic energy are delivered for blood-brain barrier opening throughout the brain.
Hughes, Alec; Hynynen, Kullervo
2017-08-03
The use of a phased array of ultrasound transducer elements to sonicate through the skull has opened the way for new treatments and the delivery of therapeutics beyond the blood-brain barrier. The limited steering range of current clinical devices, particularly at higher frequencies, limits the regions of the brain that are considered treatable by ultrasound. A new array design is introduced that allows for high levels of beam steering and increased transmission throughout the brain. These improvements are achieved using concave transducers normal to the outer-skull surface in a patient-specific configuration to target within the skull, so that the far-field of each beam is within the brain. It is shown that by using pulsed ultrasound waves timed to arrive in-phase at the desired target, sufficient levels of acoustic energy are delivered for blood-brain barrier opening throughout the brain.
Diagnostic and interventional musculoskeletal ultrasound: part 1. Fundamentals.
Smith, Jay; Finnoff, Jonathan T
2009-01-01
Musculoskeletal ultrasound involves the use of high-frequency sound waves to image soft tissues and bony structures in the body for the purposes of diagnosing pathology or guiding real-time interventional procedures. Recently, an increasing number of physicians have integrated musculoskeletal ultrasound into their practices to facilitate patient care. Technological advancements, improved portability, and reduced costs continue to drive the proliferation of ultrasound in clinical medicine. This increased interest creates a need for education pertaining to all aspects of musculoskeletal ultrasound. The primary purpose of this article is to review diagnostic ultrasound technology and its potential clinical applications in the evaluation and treatment of patients with neurologic and musculoskeletal disorders. After reviewing this article, physicians should be able to (1) list the advantages and disadvantages of ultrasound compared with other available imaging modalities, (2) describe how ultrasound machines produce images using sound waves, (3) discuss the steps necessary to acquire and optimize an ultrasound image, (4) understand the different ultrasound appearances of tendons, nerves, muscles, ligaments, blood vessels, and bones, and (5) identify multiple applications for diagnostic and interventional musculoskeletal ultrasound in musculoskeletal practice. Part 1 of this 2-part article reviews the fundamentals of clinical ultrasonographic imaging, including relevant physics, equipment, training, image optimization, and scanning principles for diagnostic and interventional purposes.
The Effects of Ultrasound on Biological Systems: Site
NASA Astrophysics Data System (ADS)
El-Karmi, Anan M.
Earlier studies (Dinno et al., Ultrasound Med. Biol. 15:461 -470; 1989) demonstrated that ultrasound at therapeutic intensities causes large increases in total conductance (G_{rm t}) of frog skin. These changes were attributed to non-thermal mechanisms, primarily, cavitation. In this study, the site(s) and mechanism(s) of action of ultrasound for the increase in G_{rm t} were examined. The reversible changes in G_{rm t } and sodium current were monitored in real time as a function of ultrasound exposure. Amiloride, a sodium channel blocker, was used to differentiate between cellular (G_{rm c}) and paracellular (G_{rm s}) pathways in the presence and absence of ultrasound. No significant changes were detected in G_ {rm c}. However, changes in G _{rm s} were significant. These results demonstrate that most of the increase in G _{rm t} due to ultrasound is taking place in the paracellular pathways. Sodium channels were not significantly affected by ultrasound. Thus, the changes in G_{rm c} are not specific. The effects of ultrasound were examined in the presence of radical scavengers and antioxidants. The increase in G_{rm t} due to ultrasound was significantly minimized in the presence of cystamine, cysteamine, and sodium ascorbate. This demonstrates that free radicals and other reactive species generated by cavitation are causing the increase in G_ {rm t}, possibly by acting from inside the cells. Radical scavengers and antioxidants are providing protection from oxidative damage but are not involved in the recovery of G_{ rm t} towards steady state values after sonication. The role of Ca^{2+} in the effects of ultrasound was examined since many of the cellular reactions involved in tissue recovery are dependent on the intracellular availability of free Ca^{2+}. The percentage increase in G_{rm t} in the presence of Ca^{2+} was larger than in its absence (140% vs. 27%). The time constant for G_{rm t} to return to steady state was longer in calcium-free solutions (122
Ultrasound is a type of imaging. It uses high-frequency sound waves to look at organs and ... liver, and other organs. During pregnancy, doctors use ultrasound to view the fetus. Unlike x-rays, ultrasound ...
Ultrasound physics and instrumentation for pathologists.
Lieu, David
2010-10-01
Interest in pathologist-performed ultrasound-guided fine-needle aspiration is increasing. Educational courses discuss clinical ultrasound and biopsy techniques but not ultrasound physics and instrumentation. To review modern ultrasound physics and instrumentation to help pathologists understand the basis of modern ultrasound. A review of recent literature and textbooks was performed. Ultrasound physics and instrumentation are the foundations of clinical ultrasound. The key physical principle is the piezoelectric effect. When stimulated by an electric current, certain crystals vibrate and produce ultrasound. A hand-held transducer converts electricity into ultrasound, transmits it into tissue, and listens for reflected ultrasound to return. The returning echoes are converted into electrical signals and used to create a 2-dimensional gray-scale image. Scanning at a high frequency improves axial resolution but has low tissue penetration. Electronic focusing moves the long-axis focus to depth of the object of interest and improves lateral resolution. The short-axis focus in 1-dimensional transducers is fixed, which results in poor elevational resolution away from the focal zone. Using multiple foci improves lateral resolution but degrades temporal resolution. The sonographer can adjust the dynamic range to change contrast and bring out subtle masses. Contrast resolution is limited by processing speed, monitor resolution, and gray-scale perception of the human eye. Ultrasound is an evolving field. New technologies include miniaturization, spatial compound imaging, tissue harmonics, and multidimensional transducers. Clinical cytopathologists who understand ultrasound physics, instrumentation, and clinical ultrasound are ready for the challenges of cytopathologist-performed ultrasound-guided fine-needle aspiration and core-needle biopsy in the 21st century.
Ultrasound-Assisted Hot Air Drying of Foods
NASA Astrophysics Data System (ADS)
Mulet, Antonio; Cárcel, Juan Andrés; García-Pérez, José Vicente; Riera, Enrique
This chapter deals with the application of power ultrasound, also named high-intensity ultrasound, in the hot air drying of foods. The aim of ultrasound-assisted drying is to overcome some of the limitations of traditional convective drying systems, especially by increasing drying rate without reducing quality attributes. The effects of ultrasound on drying rate are responsible for some of the phenomena produced in the internal and/or external resistance to mass transfer.
MedlinePlus Videos and Cool Tools
Ultrasound is a useful procedure for monitoring the baby's development in the uterus. Ultrasound uses inaudible sound waves to produce a two- ... sound waves and appear dark or black. An ultrasound can supply vital information about a mother's pregnancy ...
[Occupational risk caused by ultrasound in medicine].
Magnavita, N; Fileni, A
1994-01-01
Ultrasound (US) is extensively used in the medical field for its therapeutic and diagnostic applications. US units are commonly found in hospitals and clinics of all sizes, and a growing number of medical staff such as doctors and nurses are exposed to hand-transmitted ultrasound waves in their work-place. This review discusses the available information on the occupational risk of the operators using diagnostic and therapeutic ultrasound devices. The new occupational groups of medical workers who use ultrasound (diagnostic, surgical, sterilization, and physiotherapeutic) equipment are exposed to contact ultrasound waves. Contact ultrasound -- i.e., no airspace between the energy source and the biological tissue -- is much more hazardous than exposure to airborne ultrasound because air transmits less than one percent of this kind of energy. In spite of being a non-ionizing radiation with an excellent safety record, US is likely to induce some changes in the exposed organ. Recent Russian studies indicate that the hospital workers who have been long exposed to ultrasound at work may develop neurovascular dose-dependent disorders of the peripheral nervous system in the form of the angiodystonic syndrome of vegetative polyneuritis of the hands. In some Scandinavian studies, female physiotherapists (exposed to ultrasound and short waves) exhibit increased rate of spontaneous abortions and congenital malformations, but no definite conclusion can be drawn on the basis of these results alone. Trends in exposure for diagnostic ultrasound equipment over the last two decades show a continuous increase. While there is no reason for alarm, there is a growing need for avoiding unnecessary exposure to medical workers.
Ultrasound assisted biogas production from landfill leachate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oz, Nilgün Ayman, E-mail: nilgunayman@comu.edu.tr; Yarimtepe, Canan Can
Highlights: • Effect of low frequency ultrasound pretreatment on leachate was investigated. • Three different ultrasound energy inputs (200, 400 and 600 W/l) was applied. • Low-frequency ultrasound treatment increased soluble COD in landfill leachate. • Application of ultrasound to leachate increased biogas production about 40%. • Application of ultrasound to leachate increased total methane production rate about 20%. - Abstract: The aim of this study is to increase biogas production and methane yield from landfill leachate in anaerobic batch reactors by using low frequency ultrasound as a pretreatment step. In the first part of the study, optimum conditions formore » solubilization of organic matter in leachate samples were investigated using various sonication durations at an ultrasound frequency of 20 kHz. The level of organic matter solubilization during ultrasonic pretreatment experiments was determined by calculating the ratio of soluble chemical oxygen demand (sCOD) to total chemical oxygen demand (tCOD). The sCOD/tCOD ratio was increased from 47% in raw leachate to 63% after 45 min sonication at 600 W/l. Non-parametric Friedman’s test indicated that ultrasonic pretreatment has a significant effect on sCOD parameter for leachate (p < 0.05). In the second part of the study, anaerobic batch reactors were operated for both ultrasonically pretreated and untreated landfill leachate samples in order to assess the effect of sonication on biogas and methane production rate. In anaerobic batch reactor feed with ultrasonically pretreated leachate, 40% more biogas was obtained compared to the control reactor. For statistical analysis, Mann–Whitney U test was performed to compare biogas and methane production rates for raw and pretreated leachate samples and it has been found that ultrasonic pretreatment significantly enhanced biogas and methane production rates from leachate (p < 0.05) in anaerobic batch reactors. The overall results showed that low
Rankin, S; Morii, N; Narumiya, S; Rozengurt, E
1994-11-14
In this study we examined the role of rho p21 in neuropeptide-stimulated tyrosine phosphorylation. Intact Swiss 3T3 cells were treated with the Clostridium botulinum C3 exoenzyme which specifically ADP ribosylates and inactivates rho p21. C3 exoenzyme treatment of cells caused a marked decrease in both bombesin- and endothelin-stimulated tyrosine phosphorylation of multiple proteins, including p125 focal adhesion kinase (FAK) and paxillin. Our results suggest that rho p21 is a component of the signal transduction pathway linking seven transmembrane domain receptors with tyrosine phosphorylation and cytoskeletal events.
Basson, M D; Zeng, B; Wang, S
2015-10-01
Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means
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.
Synergistic effect of ultrasound and PEI on DNA transfection in vitro
Deshpande, Mangesh C.; Prausnitz, Mark R.
2007-01-01
Ultrasound and poly(ethylenimine) (PEI) have each separately been shown to increase DNA transfection efficiency. This study tested the hypothesis that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. This in vitro study assessed transfection efficiency of two different DNA plasmids encoding green fluorescent protein and firefly luciferase in two different cells types, a primary culture of human aortic smooth muscle cells and an immortal line of human prostrate cancer cells. We found that ultrasound sonication increased transfection up to 18-fold, DNA complexation with PEI increased transfection up to 90-fold, and the combination of ultrasound and PEI synergistically increased transfection up to 200-fold, which resulted in reporter gene expression by 34% of cells. Kinetic measurements found that the effects of ultrasound alone acted quickly, whereas increased transfection by PEI either alone or in combination with ultrasound strongly benefited from a 4-h incubation with the DNA plasmid after sonication. Although serum reduced absolute expression levels, it did not affect the relative increase in transfection when ultrasound was added to PEI enhancement. Flow cytometry measurements showed that sonication increased intracellular uptake of labelled DNA complexed to PEI by 55% relative to PEI complexation alone. Electrophoresis assay showed no damage to DNA or PEI-DNA complexes after sonication. Overall, these results suggest that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. PMID:17258835
Sun, Xiacheng; Cao, Haiyan; Zhan, Lei; Yin, Chun; Wang, Gang; Liang, Ping; Li, Jibin; Wang, Zhe; Liu, Bingrong; Huang, Qichao; Xing, Jinliang
2018-07-01
Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca 2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Pulse Compression Techniques for Laser Generated Ultrasound
NASA Technical Reports Server (NTRS)
Anastasi, R. F.; Madaras, E. I.
1999-01-01
Laser generated ultrasound for nondestructive evaluation has an optical power density limit due to rapid high heating that causes material damage. This damage threshold limits the generated ultrasound amplitude, which impacts nondestructive evaluation inspection capability. To increase ultrasound signal levels and improve the ultrasound signal-to-noise ratio without exceeding laser power limitations, it is possible to use pulse compression techniques. The approach illustrated here uses a 150mW laser-diode modulated with a pseudo-random sequence and signal correlation. Results demonstrate the successful generation of ultrasonic bulk waves in aluminum and graphite-epoxy composite materials using a modulated low-power laser diode and illustrate ultrasound bandwidth control.
2006-01-01
Executive Summary Objective The aim of this review was to assess the clinical utility of portable bladder ultrasound. Clinical Need: Target Population and Condition Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 m
Diagnostic and interventional musculoskeletal ultrasound: part 2. Clinical applications.
Smith, Jay; Finnoff, Jonathan T
2009-02-01
Musculoskeletal ultrasound involves the use of high-frequency sound waves to image soft tissues and bony structures in the body for the purposes of diagnosing pathology or guiding real-time interventional procedures. Recently, an increasing number of physicians have integrated musculoskeletal ultrasound into their practices to facilitate patient care. Technological advancements, improved portability, and reduced costs continue to drive the proliferation of ultrasound in clinical medicine. This increased interest creates a need for education pertaining to all aspects of musculoskeletal ultrasound. The primary purpose of this article is to review diagnostic ultrasound technology and its potential clinical applications in the evaluation and treatment of patients with neurological and musculoskeletal disorders. After reviewing this article, physicians should be able to (1) list the advantages and disadvantages of ultrasound compared to other available imaging modalities; (2) describe how ultrasound machines produce images using sound waves; (3) discuss the steps necessary to acquire and optimize an ultrasound image; (4) understand the difference ultrasound appearances of tendons, nerves, muscles, ligaments, blood vessels, and bones; and (5) identify multiple applications for diagnostic and interventional musculoskeletal ultrasound. Part 2 of this 2-part article will focus on the clinical applications of musculoskeletal ultrasound in clinical practice, including the ultrasonographic appearance of normal and abnormal tissues as well as specific diagnostic and interventional applications in major body regions.
Ultrasound Imaging of the Musculoskeletal System.
Cook, Cristi R
2016-05-01
Musculoskeletal ultrasound is a rapidly growing field within veterinary medicine. Ultrasound for musculoskeletal disorders has been commonly used in equine and human medicine and is becoming more commonly performed in small animal patients due to the increase in the recognition of soft tissue injuries. Ultrasound is widely available, cost-effective, but technically difficult to learn. Advantages of musculoskeletal ultrasound are the opposite limb is commonly used for comparison to evaluate symmetry of the tendinous structures and the ease of repeat examinations to assess healing. The article discusses the major areas of shoulder, stifle, iliopsoas, gastrocnemius, and musculoskeletal basics. Copyright © 2016 Elsevier Inc. All rights reserved.
Stone, Rebecca L; Baggerly, Keith A; Armaiz-Pena, Guillermo N; Kang, Yu; Sanguino, Angela M; Thanapprapasr, Duangmani; Dalton, Heather J; Bottsford-Miller, Justin; Zand, Behrouz; Akbani, Rehan; Diao, Lixia; Nick, Alpa M; DeGeest, Koen; Lopez-Berestein, Gabriel; Coleman, Robert L; Lutgendorf, Susan; Sood, Anil K
2014-01-01
This investigation describes the clinical significance of phosphorylated focal adhesion kinase (FAK) at the major activating tyrosine site (Y397) in epithelial ovarian cancer (EOC) cells and tumor-associated endothelial cells. FAK gene amplification as a mechanism for FAK overexpression and the effects of FAK tyrosine kinase inhibitor VS-6062 on tumor growth, metastasis, and angiogenesis were examined. FAK and phospho-FAKY397 were quantified in tumor (FAK-T; pFAK-T) and tumor-associated endothelial (FAK-endo; pFAK-endo) cell compartments of EOCs using immunostaining and qRT-PCR. Associations between expression levels and clinical variables were evaluated. Data from The Cancer Genome Atlas were used to correlate FAK gene copy number and expression levels in EOC specimens. The in vitro and in vivo effects of VS-6062 were assayed in preclinical models. FAK-T and pFAK-T overexpression was significantly associated with advanced stage disease and increased microvessel density (MVD). High MVD was observed in tumors with elevated endothelial cell FAK (59%) and pFAK (44%). Survival was adversely affected by FAK-T overexpression (3.03 vs 2.06 y, P = 0.004), pFAK-T (2.83 vs 1.78 y, P < 0.001), and pFAK-endo (2.33 vs 2.17 y, P = 0.005). FAK gene copy number was increased in 34% of tumors and correlated with expression levels (P < 0.001). VS-6062 significantly blocked EOC and endothelial cell migration as well as endothelial cell tube formation in vitro. VS-6062 reduced mean tumor weight by 56% (P = 0.005), tumor MVD by 40% (P = 0.0001), and extraovarian metastasis (P < 0.01) in orthotopic EOC mouse models. FAK may be a unique therapeutic target in EOC given the dual anti-angiogenic and anti-metastatic potential of FAK inhibitors. PMID:24755674
Engholm, Mathias; Beers, Christopher; Bouzari, Hamed; Jensen, Jørgen Arendt; Thomsen, Erik Vilain
2018-08-01
The purpose of this work is to investigate compound lenses for row-column-addressed (RCA) ultrasound transducers for increasing the field-of-view (FOV) to a curvilinear volume region, while retaining a flat sole to avoid trapping air between the transducer sole and the patient, which would otherwise lead to unwanted reflections. The primary motivation behind this research is to develop a RCA ultrasound transducer for abdominal or cardiac imaging, where a curvilinear volume region is a necessity. RCA transducers provide 3-D ultrasound imaging with fewer channels than fully-addressed 2-D arrays (2N instead of N 2 ), but they have inherently limited FOV. By increasing the RCA FOV, these transducers can be used for the same applications as fully-addressed transducers while retaining the same price range as conventional 2-D imaging due to the lower channel count. Analytical and finite element method (FEM) models were employed to evaluate design options. Composite materials were developed by loading polymers with inorganic powders to satisfy the corresponding speed of sound and specific acoustical impedance requirements. A Bi 2 O 3 powder with a density of 8.9g/cm 3 was used to decrease the speed of sound of a room temperature vulcanizing (RTV) silicone, RTV615, from 1.03mm/μs to 0.792mm/μs. Using micro-balloons in RTV615 and a urethane, Hapflex 541, their speeds of sound were increased from 1.03mm/μs to 1.50mm/μs and from 1.52mm/μs to 1.93mm/μs, respectively. A diverging add-on lens was fabricated of a Bi 2 O 3 loaded RTV615 and an unloaded Hapflex 541. The lens was tested using a RCA probe, and a FOV of 32.2° was measured from water tank tests, while the FEM model yielded 33.4°. A wire phantom with 0.15mm diameter wires was imaged at 3MHz down to a depth of 14cm using a synthetic aperture imaging sequence with single element transmissions. The beamformed image showed that wires outside the array footprint were visible, demonstrating the increased FOV. Copyright
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant
Spinal curvature measurement by tracked ultrasound snapshots.
Ungi, Tamas; King, Franklin; Kempston, Michael; Keri, Zsuzsanna; Lasso, Andras; Mousavi, Parvin; Rudan, John; Borschneck, Daniel P; Fichtinger, Gabor
2014-02-01
Monitoring spinal curvature in adolescent kyphoscoliosis requires regular radiographic examinations; however, the applied ionizing radiation increases the risk of cancer. Ultrasound imaging is favored over radiography because it does not emit ionizing radiation. Therefore, we tested an ultrasound system for spinal curvature measurement, with the help of spatial tracking of the ultrasound transducer. Tracked ultrasound was used to localize vertebral transverse processes as landmarks along the spine to measure curvature angles. The method was tested in two scoliotic spine models by localizing the same landmarks using both ultrasound and radiographic imaging and comparing the angles obtained. A close correlation was found between tracked ultrasound and radiographic curvature measurements. Differences between results of the two methods were 1.27 ± 0.84° (average ± SD) in an adult model and 0.96 ± 0.87° in a pediatric model. Our results suggest that tracked ultrasound may become a more tolerable and more accessible alternative to radiographic spine monitoring in adolescent kyphoscoliosis. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
WE-AB-206-01: Diagnostic Ultrasound Imaging Quality Assurance
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zagzebski, J.
The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environmentmore » with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.« less
Ultrasound: biological effects and industrial hygiene concerns.
Wiernicki, C; Karoly, W J
1985-09-01
Due to the increased use of high intensity ultrasonic devices, there is now a greater risk of worker exposure to ultrasonic radiation than there was in the past. Exposure to high power ultrasound may produce adverse biological effects. High power ultrasound, characterized by high intensity outputs at frequencies of 20-100 kHz, has a wide range of applications throughout industry. Future applications may involve equipment with higher energy outputs. Contact ultrasound, i.e., no airspace between the energy source and the biological tissue, is significantly more hazardous than exposure to airborne ultrasound because air transmits less than one percent of the energy. This paper discusses biological effects associated with overexposure to ultrasound, exposure standards proposed for airborne and contact ultrasound, industrial hygiene controls that can be employed to minimize exposure, and the instrumentation that is required for evaluating exposures.
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
NASA Astrophysics Data System (ADS)
Pereira, Tatiana Aparecida; Ramos, Danielle Nishida; Lopez, Renata F. V.
2017-03-01
Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium.
Solubilization of bovine gelatin using power ultrasound: gelation without heating.
Farahnaky, Asgar; Zendeboodi, Fatemeh; Azizi, Rezvan; Mesbahi, Gholamreza; Majzoobi, Mahsa
2017-04-01
The aim of this study was to investigate the efficacy of power ultrasound without using any heating stage in solubilizeing gelatin dispersions, and to characterize the mechanical and microstructural properties of the resulting gels using texture analysis and scanning electron microscopy, respectively. Usually to prepare a gel from gelatin, a primary heating stage of at about 40C or above is required to solubilize gelatin macromolecules. In this study solubilizing gelatin dispersions using power ultrasound without any heating was successfully performed. For solubilising gelatin, an ultrasound equipment with a frequency of 20 kHz, amplitude of 100% and power range of 50-150 W was used. Aqueous gelatin dispersions (4% w/v) were subjected to ultrasound for different times (40-240 s) at a constant temperature of 13C. Applying ultrasound to gelatin dispersions caused increases in water absorption and water solubility of the hydrocolloid. The textural parameters of the resulting gelatin gels, increased with increasing time and power of ultrasound. Moreover, a generalized Maxwell model with three elements was used for calculating relaxation times of the gels. The microstructural observations by SEM showed that the structural cohesiveness of the gels increased by increasing ultrasonication time. Ultrasound-assisted solubilization of gelatin can have emerging implications for industrial uses in pharmaceuticals, food and non-food systems. Usually to prepare a gel from gelatin, a primary heating stage of at about 40C or above is required to solubilize gelatin macromolecules. Therefore, the use of gelatin as a hydrocolloid in food processings or pharmaceutical formulations which lack a heating step has been a technological and practical challenge. In this study solubilizing gelatin dispersions using power ultrasound without any heating was successfully performed. Ultrasound-assisted solubilisation of gelatin can have emerging implications for industrial uses in pharmaceuticals
... the patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... perform an ultrasound-guided biopsy . Because ultrasound provides real-time images, it is often used to guide biopsy ...
Nicholson, Stuart F.; Nimrod, Carl A.
1988-01-01
This article addresses the current indications for an obstetric ultrasound and describes the findings that it is reasonable to expect when reading an ultrasound report. The authors discuss several common obstetrical problems focussing the attention on the usefulness of the imaging information. Finally, they provide a glimpse into the future direction of obstetric ultrasound by discussing vaginal scanning, Doppler assessment of fetal blood flow, and routine ultrasound in pregnancy. PMID:21253229
Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.
Xenariou, Stefania; Liang, Hai-Dong; Griesenbach, Uta; Zhu, Jie; Farley, Raymond; Somerton, Lucinda; Singh, Charanjit; Jeffery, Peter K; Scheule, Ronald K; Cheng, Seng H; Geddes, Duncan M; Blomley, Martin; Alton, Eric W F W
2010-01-01
The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.
Temperature Changes During Therapeutic Ultrasound in the Precooled Human Gastrocnemius Muscle
Rimington, Stephanie J.; Draper, David O.; Durrant, Earlene; Fellingham, Gilbert
1994-01-01
Therapeutic ultrasound is frequently employed as a deep heating rehabilitation modality. It is administered in one of three ways: a) ultrasound with no preceding treatment, b) ultrasound on preheated tissues, or c) ultrasound on precooled tissues. The purpose of this study was to investigate the effect of ultrasound treatments on the tissue temperature rise of precooled human gastrocnemius muscle. Sixteen male subjects had a 23-gauge hypodermic needle microprobe inserted 3 cm deep into the medial aspect of their anesthetized gastrocnemius muscles. Data were gathered on each subject for one of two randomly assigned treatments: a) ultrasound treatment on precooled tissue, or b) ultrasound with no preceding treatment. Each treatment consisted of ultrasound delivered topically at 1.5 watts/cm2 in a continuous mode for 10 minutes. Ultrasound was applied in an overlapping longitudinal motion at 4 cm/s, with temperature readings recorded at 30-second intervals. We discovered a difference between the two treatment methods [t(14) = 16.26, p < .0001]. Ultrasound alone increased tissue temperature an average of 2°C, whereas ultrasound preceded by 15 minutes of ice did not increase tissue temperature even to the original baseline level. We concluded that, at a depth of 3 cm, ultrasound alone provided a greater heating effect than ultrasound preceded by an ice treatment. PMID:16558295
Musculoskeletal ultrasound in rheumatology in Korea: targeted ultrasound initiative survey.
Kang, Taeyoung; Wakefield, Richard J; Emery, Paul
2016-04-01
In collaboration with the Targeted Ultrasound Initiative (TUI), to conduct the first study in Korea to investigate current practices in ultrasound use among Korean rheumatologists. We translated the TUI Global Survey into Korean and added questions to better understand the specific challenges facing rheumatologists in Korea. To target as many rheumatologists in Korea as possible, we created an on-line version of this survey, which was conducted from March to April 2013. Rheumatologists are in charge of ultrasound in many Korean hospitals. Rheumatologists in hospitals and private clinics use ultrasound to examine between one and five patients daily; they use ultrasound for diagnosis more than monitoring and receive compensation of about US$30-50 per patient. There are marked differences in the rates of ultrasound usage between rheumatologists who work in private practice compared with tertiary hospitals. Korean rheumatologists not currently using ultrasound in their practice appear eager to do so. This survey provides important insights into the current status of ultrasound in rheumatology in Korea and highlights several priorities; specifically, greater provision of formal training, standardization of reporting and accrual of greater experience among ultrasound users. If these needs are addressed, all rheumatology departments in Korea are likely to use ultrasound or have access to it in the future. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
An ultrasound transient elastography system with coded excitation.
Diao, Xianfen; Zhu, Jing; He, Xiaonian; Chen, Xin; Zhang, Xinyu; Chen, Siping; Liu, Weixiang
2017-06-28
Ultrasound transient elastography technology has found its place in elastography because it is safe and easy to operate. However, it's application in deep tissue is limited. The aim of this study is to design an ultrasound transient elastography system with coded excitation to obtain greater detection depth. The ultrasound transient elastography system requires tissue vibration to be strictly synchronous with ultrasound detection. Therefore, an ultrasound transient elastography system with coded excitation was designed. A central component of this transient elastography system was an arbitrary waveform generator with multi-channel signals output function. This arbitrary waveform generator was used to produce the tissue vibration signal, the ultrasound detection signal and the synchronous triggering signal of the radio frequency data acquisition system. The arbitrary waveform generator can produce different forms of vibration waveform to induce different shear wave propagation in the tissue. Moreover, it can achieve either traditional pulse-echo detection or a phase-modulated or a frequency-modulated coded excitation. A 7-chip Barker code and traditional pulse-echo detection were programmed on the designed ultrasound transient elastography system to detect the shear wave in the phantom excited by the mechanical vibrator. Then an elasticity QA phantom and sixteen in vitro rat livers were used for performance evaluation of the two detection pulses. The elasticity QA phantom's results show that our system is effective, and the rat liver results show the detection depth can be increased more than 1 cm. In addition, the SNR (signal-to-noise ratio) is increased by 15 dB using the 7-chip Barker coded excitation. Applying 7-chip Barker coded excitation technique to the ultrasound transient elastography can increase the detection depth and SNR. Using coded excitation technology to assess the human liver, especially in obese patients, may be a good choice.
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
WE-AB-206-02: ACR Ultrasound Accreditation: Requirements and Pitfalls
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walter, J.
The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environmentmore » with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.« less
Roycroft, Alice; Szabó, András; Bahm, Isabel; Daly, Liam; Charras, Guillaume; Parsons, Maddy; Mayor, Roberto
2018-06-04
Contact inhibition of locomotion is defined as the behavior of cells to cease migrating in their former direction after colliding with another cell. It has been implicated in multiple developmental processes and its absence has been linked to cancer invasion. Cellular forces are thought to govern this process; however, the exact role of traction through cell-matrix adhesions and tension through cell-cell adhesions during contact inhibition of locomotion remains unknown. Here we use neural crest cells to address this and show that cell-matrix adhesions are rapidly disassembled at the contact between two cells upon collision. This disassembly is dependent upon the formation of N-cadherin-based cell-cell adhesions and driven by Src and FAK activity. We demonstrate that the loss of cell-matrix adhesions near the contact leads to a buildup of tension across the cell-cell contact, a step that is essential to drive cell-cell separation after collision. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Supercooling of Water Controlled by Nanoparticles and Ultrasound
NASA Astrophysics Data System (ADS)
Cui, Wei; Jia, Lisi; Chen, Ying; Li, Yi'ang; Li, Jun; Mo, Songping
2018-05-01
Nanoparticles, including Al2O3 and SiO2, and ultrasound were adopted to improve the solidification properties of water. The effects of nanoparticle concentration, contact angle, and ultrasonic intensity on the supercooling degree of water were investigated, as well as the dispersion stability of nanoparticles in water during solidification. Experimental results show that the supercooling degree of water is reduced under the combined effect of ultrasound and nanoparticles. Consequently, the reduction of supercooling degree increases with the increase of ultrasonic intensity and nanoparticle concentration and decrease of contact angle of nanoparticles. Moreover, the reduction of supercooling degree caused by ultrasound and nanoparticles together do not exceed the sum of the supercooling degree reductions caused by ultrasound and nanoparticles separately; the reduction is even smaller than that caused by ultrasound individually under certain conditions of controlled nanoparticle concentration and contact angle and ultrasonic intensity. The dispersion stability of nanoparticles during solidification can be maintained only when the nanoparticles and ultrasound together show a superior effect on reducing the supercooling degree of water to the single operation of ultrasound. Otherwise, the aggregation of nanoparticles appears in water solidification, which results in failure. The relationships among the meaningful nanoparticle concentration, contact angle, and ultrasonic intensity, at which the requirements of low supercooling and high stability could be satisfied, were obtained. The control mechanisms for these phenomena were analyzed.
Needle tip visibility in 3D ultrasound images
NASA Astrophysics Data System (ADS)
Arif, Muhammad; Moelker, Adriaan; van Walsum, Theo
2017-03-01
Needle visibility is of crucial importance for ultrasound guided interventional procedures. However, several factors, such as shadowing by bone or gas and tissue echogenic properties similar to needles, may compromise needle visibility. Additionally, small angle between the ultrasound beam and the needle, as well as small gauged needles may reduce visibility. Variety in needle tips design may also affect needle visibility. Whereas several studies have investigated needle visibility in 2D ultrasound imaging, no data is available for 3D ultrasound imaging, a modality that has great potential for image guidance interventions1. In this study, we evaluated needle visibility using a 3D ultrasound transducer. We examined different needles in a tissue mimicking liver phantom at three angles (200, 550 and 900) and quantify their visibility. The liver phantom was made by 5% polyvinyl alcohol solution containing 1% Silica gel particles to act as ultrasound scattering particles. We used four needles; two biopsy needles (Quick core 14G and 18G), one Ablation needle (Radiofrequency Ablation 17G), and Initial puncture needle (IP needle 17G). The needle visibility was quantified by calculating contrast to noise ratio. The results showed that the visibility for all needles were almost similar at large angles. However the difference in visibility at lower angles is more prominent. Furthermore, the visibility increases with the increase in angle of ultrasound beam with needles.
Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan R.
2015-01-01
Background Ultrasound can increase tissue blood flow in part through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation, and sought to characterize the biologic mediators. Methods and Results Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in non-ischemic mice after unilateral 10 min exposure to intermittent ultrasound alone (mechanical index [MI] 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 I.V.). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (p<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3-fold and 10-fold higher than control for MI 0.6 and 1.3, respectively; p<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase (eNOS) attenuated flow augmentation produced by ultrasound and microbubbles by 70% (p<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide (NO) production and muscle phospho-eNOS increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40–50% reduction in flow), ultrasound (MI 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control non-ischemic limb. Conclusions Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of eNOS. PMID:25834183
Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R
2015-04-01
Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; P<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (P<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart
Ultrasound pretreatment of filamentous algal biomass for enhanced biogas production.
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.
Power ultrasound-assisted cleaner leather dyeing technique: influence of process parameters.
Sivakumar, Venkatasubramanian; Rao, Paruchuri Gangadhar
2004-03-01
The application of power ultrasound to leather processing has a significant role in the concept of "clean technology" for leather production. The effect of power ultrasound in leather dyeing has been compared with dyeing in the absence of ultrasound and conventional drumming. The power ultrasound source used in these experiments was ultrasonic cleaner (150 W and 33 kHz). The effect of various process parameters such as amount of dye offer, temperature, and type of dye has been experimentally found out. The effect of presonication of dye solution as well as leather has been studied. Experiments at ultrasonic bath temperature were carried out to find out the combined thermal as well as stirring effects of ultrasound. Dyeing in the presence of ultrasound affords about 37.5 (1.8 times) difference as increase in % dye exhaustion or about 50% decrease in the time required for dyeing compared to dyeing in the absence of ultrasound for 4% acid red dye. About 29 (1.55 times) increase in % dye exhaustion or 30% reduction in time required for dyeing was observed using ultrasound at stationary condition compared with conventional dynamic drumming conditions. The effect of ultrasound at constant temperature conditions with a control experiment has also been studied. The dye exhaustion increases as the temperature increases (30-60 degrees C) and better results are observed at higher temperature due to the use of ultrasound. Presonication of dye solution or crust leather prior to the dyeing process has no significant improvement in dye exhaustion, suggesting ultrasound effect is realized when it is applied during the dyeing process. The results indicate that 1697 and 1416 ppm of dye can be reduced in the spent liquor due to the use of ultrasound for acid red (for 100 min) and acid black (for 3 h) dyes, respectively, thereby reducing the pollution load in the effluent stream. The color yield of the leather as inferred from the reflectance measurement indicates that dye offer can
Novel ultrasound method to reposition kidney stones
Shah, Anup; Owen, Neil R.; Lu, Wei; Cunitz, Bryan W.; Kaczkowski, Peter J.; Harper, Jonathan D.; Bailey, Michael R.; Crum, Lawrence A.
2011-01-01
The success of surgical management of lower pole stones is principally dependent on stone fragmentation and residual stone clearance. Choice of surgical method depends on stone size, yet all methods are subject to post-surgical complications resulting from residual stone fragments. Here we present a novel method and device to reposition kidney stones using ultrasound radiation force delivered by focused ultrasound and guided by ultrasound imaging. The device couples a commercial imaging array with a focused annular array transducer. Feasibility of repositioning stones was investigated by implanting artificial and human stones into a kidney-mimicking phantom that simulated a lower pole and collecting system. During experiment, stones were located by ultrasound imaging and repositioned by delivering short bursts of focused ultrasound. Stone motion was concurrently monitored by fluoroscopy, ultrasound imaging, and video photography, from which displacement and velocity were estimated. Stones were seen to move immediately after delivering focused ultrasound and successfully repositioned from the lower pole to the collecting system. Estimated velocities were on the order of 1 cm/s. This in vitro study demonstrates a promising modality to facilitate spontaneous clearance of kidney stones and increased clearance of residual stone fragments after surgical management. PMID:20967437
Sudoł-Szopińska, Iwona; Schueller-Weidekamm, Claudia; Plagou, Athena; Teh, James
2017-09-01
Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.
The chitinase-like protein YKL-40 increases mucin5AC production in human bronchial epithelial cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Chunyi; Li, Qi; Zhou, Xiangdong, E-mail: zxd999@263.net
2013-11-01
Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. However, the regulatory mechanisms that mediate excessive mucin production remain elusive. Recently, the level of YKL-40, a chitinase-like protein, has been found to be significantly increased in chronic inflammatory airway diseases and has been shown to be associated with the severity of these diseases. In this study, we sought to explore the effect of YKL-40 on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in this process. We found that elevated YKL-40 levels increased the mRNA and protein expression of MUC5ACmore » in a dose- and time-dependent manner, in association with the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB), reflecting their activation. These responses were significantly suppressed by the knockdown of protease-activating receptor 2 (PAR2) with specific small interfering RNA or the inhibitors of ERK and NF-κB. YKL-40-induced MUC5AC overproduction was also effectively attenuated by the inhibitor of focal adhesion kinase (FAK). Taken together, these results imply that YKL-40 can stimulate excessive MUC5AC production through PAR2- and FAK-mediated mechanisms. - Highlights: • MUC5AC is the major secreted mucin in chronic inflammatory airway diseases. • YKL-40 is a prototype of the chitinase-like protein in mammals. • YKL-40 is an active player in chronic inflammatory airway diseases. • YKL-40 can increase MUC5AC production via PAR2-mediated pathway. • FAK is another candidate to mediate YKL-40-induced MUC5AC overexpression.« less
Hunger Games: Interactive Ultrasound Imaging for Learning Gastrointestinal Physiology.
Kafer, Ilana; Rennie, William; Noor, Ali; Pellerito, John S
2017-02-01
Ultrasound is playing an increasingly important role in medical student education. Although most uses of ultrasound have focused on learning purely anatomic relationships or augmentation of the physical examination, there is little documentation of the value of ultrasound as a learning tool regarding physiology alone or in association with anatomy. We devised an interactive learning session for first-year medical students using ultrasound to combine both anatomic and physiologic principles as an integration of gastrointestinal and vascular function. The incorporation of our activity, The Hunger Games, provides the foundation for a powerful integration tool for medical student education. © 2016 by the American Institute of Ultrasound in Medicine.
Sports Ultrasound: Applications Beyond the Musculoskeletal System.
Finnoff, Jonathan T; Ray, Jeremiah; Corrado, Gianmichael; Kerkhof, Deanna; Hill, John
2016-09-01
Traditionally, ultrasound has been used to evaluate musculoskeletal injuries in athletes; however, ultrasound applications extend well beyond musculoskeletal conditions, many of which are pertinent to athletes. Articles were identified in PubMed using the search terms ultrasound, echocardiogram, preparticipation physical examination, glycogen, focused assessment with sonography of trauma, optic nerve, and vocal cord dysfunction. No date restrictions were placed on the literature search. Clinical review. Level 4. Several potential applications of nonmusculoskeletal ultrasound in sports medicine are presented, including extended Focused Assessment with Sonography for Trauma (eFAST), limited echocardiographic screening during preparticipation physical examinations, assessment of muscle glycogen stores, optic nerve sheath diameter measurements in athletes with increased intracranial pressure, and assessment of vocal cord dysfunction in athletes. Ultrasound can potentially be used to assist athletes with monitoring their muscle glycogen stores and the diagnosis of multiple nonmusculoskeletal conditions within sports medicine. © 2016 The Author(s).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU andmore » SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC. - Highlights: • Pharmacological inhibition of sphingosine kinase 1/2 augments cytotoxic effects of 5-FU in HepG2 cells. • Co-administration of 5-FU and SKI-II synergistically inhibits cell proliferation, reduces cell migration and clonogenic survival and increases apoptosis induction in HepG2 cells. • The mechanism underlying
Kusuyama, Joji; Bandow, Kenjiro; Ohnishi, Tomokazu; Hisadome, Mitsuhiro; Shima, Kaori; Semba, Ichiro; Matsuguchi, Tetsuya
2017-05-15
Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone lesions such as those in rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 ( Nos1 ) and Nos2 was increased by low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts. The increase of Nos1/2 expression was abrogated by both exogenous OPN overexpression and recombinant OPN treatment, whereas it was promoted by OPN-specific siRNA and OPN antibody. Moreover, LIPUS-induced phosphorylation of focal adhesion kinase (FAK), a crucial regulator of mechanoresponses, was down-regulated by OPN treatments. OPN also attenuated hepatocyte growth factor-induced vitamin D receptor ( Vdr ) expression and platelet-derived growth factor-induced cell mobility through the repression of FAK activity. Of note, the expression of low-molecular weight protein tyrosine phosphatase (LMW-PTP), a FAK phosphatase, was increased in both OPN-treated and differentiated osteoblasts. CD44 was a specific OPN receptor for LWW-PTP induction. Consistently, the suppressive influence of OPN on osteoblast responsiveness was abrogated by LMW-PTP knockdown. Taken together, these results reveal novel functions of OPN in osteoblast physiology. © 2017 Kusuyama et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Macha, Muzafar A; Rachagani, Satyanarayana; Gupta, Suprit; Pai, Priya; Ponnusamy, Moorthy P; Batra, Surinder K; Jain, Maneesh
2013-12-01
Inadequate efficacy, high toxicity and drug resistance associated with existing chemotherapeutic agents mandate a need for novel therapeutic strategies for highly aggressive Pancreatic Cancer (PC). Guggulsterone (GS) exhibits potent anti-proliferative effects against various cancer cells and has emerged as an attractive candidate for use in complementary or preventive cancer therapies. However, the knowledge regarding the therapeutic potential of GS in PC is still limited and needs to be explored. We studied the effect of GS on PC cell growth, motility and invasion and elucidated the molecular mechanisms associated with its anti-tumor effects. Treatment of Capan1 and CD18/HPAF PC cells with GS resulted in dose- and time-dependent growth inhibition and decreased colony formation. Further, GS treatment induced apoptosis and cell cycle arrest as assessed by Annexin-V assay and FACS analysis. Increased apoptosis following GS treatment was accompanied with Bad dephosphorylation and its translocation to the mitochondria, increased Caspase-3 activation, decreased Cyclin D1, Bcl-2 and xIAP expression. Additionally, GS treatment decreased motility and invasion of PC cells by disrupting cytoskeletal organization, inhibiting activation of FAK and Src signaling and decreased MMP9 expression. More importantly, GS treatment decreased mucin MUC4 expression in Capan1 and CD18/HPAF cells through transcriptional regulation by inhibiting Jak/STAT pathway. In conclusion, our results support the utility of GS as a potential therapeutic agent for lethal PC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Macha, Muzafar A.; Rachagani, Satyanarayana; Gupta, Suprit; Pai, Priya; Ponnusamy, Moorthy P.; Batra, Surinder K.; Jain, Maneesh
2013-01-01
Inadequate efficacy, high toxicity and drug resistance associated with existing chemotherapeutic agents mandate a need for novel therapeutic strategies for highly aggressive pancreatic cancer (PC). Guggulsterone (GS) exhibits potent anti-proliferative effects against various cancer cells and has emerged as an attractive candidate for use in complementary or preventive cancer therapies. However, the knowledge regarding the therapeutic potential of GS in PC is still limited and needs to be explored. We studied the effect of GS on PC cell growth, motility and invasion and elucidated the molecular mechanisms associated with its anti-tumor effects. Treatment of Capan1 and CD18/HPAF PC cells with GS resulted in dose- and time-dependent growth inhibition and decreased colony formation. Further, GS treatment induced apoptosis and cell cycle arrest as assessed by Annexin-V assay and FACS analysis. Increased apoptosis following GS treatment was accompanied with Bad dephosphorylation and its translocation to the mitochondria, increased Caspase-3 activation, decreased Cyclin D1, Bcl-2 and xIAP expression. Additionally, GS treatment decreased motility and invasion of PC cells by disrupting cytoskeletal organization, inhibiting activation of FAK and Src signaling and decreased MMP9 expression. More importantly, GS treatment decreased mucin MUC4 expression in Capan1 and CD18/HPAF cells through transcriptional regulation by inhibiting Jak/STAT pathway. In conclusion, our results support the utility of GS as a potential therapeutic agent for lethal PC. PMID:23920124
Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots
Chernysh, Irina N.; Everbach, E. Carr; Purohit, Prashant K.; Weisel, John W.
2016-01-01
Summary Background Ultrasound accelerates tissue-type plasminogen activator (t-PA)-induced fibrinolysis of clots in vitro and in vivo. Objective To identify mechanisms for the enhancement of t-PA-induced fibrinolysis of clots. Methods Turbidity is an accurate and convenient method, not previously used, to follow the effects of ultrasound. Deconvolution microscopy was used to determine changes in structure, while fluorescence recovery after photobleaching was used to characterize the kinetics of binding/unbinding and transport. Results The ultrasound pulse repetition frequency affected clot lysis times, but there were no thermal effects. Ultrasound in the absence of t-PA produced a slight but consistent decrease in turbidity, suggesting a decrease in fibrin diameter due solely to the action of the ultrasound, likely caused by an increase in protofibril tension because of vibration from ultrasound. Changes in fibrin network structure during lysis with ultrasound were visualized in real time by deconvolution microscopy, revealing that the network becomes unstable when 30–40% of the protein in the network was digested, whereas without ultrasound, the fibrin network was digested gradually and retained structural integrity. Fluorescence recovery after photobleaching during lysis revealed that the off-rate of oligomers from digesting fibers was not much affected but the number of binding/unbinding sites was increased. Conclusions Ultrasound causes a decrease in the diameter of the fibers due to tension as a result of vibration, leading to increased binding sites for plasmin(ogen)/t-PA. The positive feedback of this structural change together with increased mixing/transport of t-PA/plasmin(ogen) is likely to account for the observed enhancement of fibrinolysis by ultrasound. PMID:25619618
Ma, Xiaobin; Wang, Danli; Yin, Michelle; Lucente, Juliet; Wang, Wenjun; Ding, Tian; Ye, Xingqian; Liu, Donghong
2017-05-01
In this study, ultrasound was applied both during and after the immobilization process and characteristics of different immobilized pectinase samples were studied. When introduced during the immobilization process, ultrasound at an intensity of 9WmL -1 for 20min increased the immobilization yield 92.28% more than the control. When introduced to the already immobilized pectinase, ultrasound at an intensity of 4.5WmL -1 for 10min increased the pectinase activity by 30.05%. Results of scanning electron microscope demonstrated that ultrasound increased surface area and loosened structures of immobilized enzymes. Higher V max and lower K m were obtained after ultrasound treatment, indicating the increased catalytic efficiency and enhanced affinity of immobilized pectinase. Furthermore, the optimum temperature and pH for free and immobilized pectinase remained unchanged at 50°C and pH 4. Thermostability, reaction stability and reusability of two ultrasound-treated pectinase enzymes slightly decreased due to structural matrix changes. Copyright © 2016 Elsevier B.V. All rights reserved.
Critical Care Ultrasound: A Review for Practicing Nephrologists.
Wilson, Jennifer G; Breyer, Kristine E W
2016-05-01
The use of point-of-care ultrasound in the intensive care unit, both for diagnostic and procedural purposes, has rapidly proliferated, and evidence supporting its use is growing. Conceptually, critical care ultrasound (CCUS) should be considered an extension of the physical examination and should not be considered a replacement for formal echocardiography or radiology-performed ultrasound. Several CCUS applications are of particular relevance to nephrologists, including focused renal ultrasound in patients at high risk for urinary tract obstruction, real-time ultrasound guidance and verification during the placement of central venous catheters, and ultrasound-augmented assessment of shock and volume status. Each of these applications has the capacity to improve outcomes in patients with acute kidney injury. Although robust evidence regarding long-term outcomes is lacking, existing data demonstrate that CCUS has the potential to improve diagnostic accuracy, expedite appropriate management, and increase safety for critically ill patients across a spectrum of pathologies. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Ultrasound in pregnancy (image)
The ultrasound has become a standard procedure used during pregnancy. It can demonstrate fetal growth and can detect increasing ... abnormalities, hydrocephalus, anencephaly, club feet, and other ... does not produce ionizing radiation and is considered ...
Point-of-Care Ultrasound: A Trend in Health Care.
Buerger, Anita M; Clark, Kevin R
2017-11-01
To discuss the current and growing use of point-of-care (POC) ultrasound in the management and care of patients. Several electronic research databases were searched to find articles that emphasized the use of POC ultrasound by health care providers who manage and treat critically ill or injured patients. Thirty-five relevant peer-reviewed journal articles were selected for this literature review. Common themes identified in the literature included the use of POC ultrasound in emergency medicine, military medicine, and remote care; comparison of POC ultrasound to other medical imaging modalities; investigation of the education and training required for nonimaging health care professionals who perform POC ultrasound in their practices; and discussion of the financial implications and limitations of POC ultrasound. POC ultrasound provides clinicians with real-time information to better manage and treat critically ill or injured patients in emergency medicine, military medicine, and remote care. In addition to providing immediate bedside diagnostic information, use of POC ultrasound has increased because of concerns regarding radiation protection. Finally, the expansion of POC ultrasound to other specialty areas requires nonimaging health care professionals to perform bedside ultrasound examinations and interpret the resulting images. Because POC ultrasound is user-dependent, adequate training is essential for all who perform and interpret the examinations. Research involving POC ultrasound will continue as innovations and confidence in ultrasound applications advance. Future research should continue to examine the broad use of POC ultrasound in patient care and management. ©2017 American Society of Radiologic Technologists.
3-D Ultrasound Vascularity Assessment for Breast Cancer Diagnosis
1998-09-01
ultrasound imaging in discriminating benign from malignant known masses . Preliminary data analyses were completed on new trials and contributions were made...specificity of ultrasound imaging in discriminating benign from malignant known masses . Increasingly we and others will look toward expanded roles in...evaluate which Doppler signals might provide discrimination of breast cancer from benign masses and to compare 2D and 3D ultrasound display modes.
Venous catheterization with ultrasound navigation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kasatkin, A. A., E-mail: ant-kasatkin@yandex.ru; Nigmatullina, A. R.; Urakov, A. L., E-mail: ant-kasatkin@yandex.ru
By ultrasound scanning it was determined that respiratory movements made by chest of healthy and sick person are accompanied by respiratory chest rise of internal jugular veins. During the exhalation of an individual diameter of his veins increases and during the breath it decreases down to the complete disappearing if their lumen. Change of the diameter of internal jugular veins in different phases can influence significantly the results of vein puncture and cauterization in patients. The purpose of this research is development of the method increasing the efficiency and safety of cannulation of internal jugular veins by the ultrasound visualization.more » We suggested the method of catheterization of internal jugular veins by the ultrasound navigation during the execution of which the puncture of venous wall by puncture needle and the following conduction of J-guide is carried out at the moment of patient’s exhalation. This method decreases the risk of complications development during catheterization of internal jugular vein due to exclusion of perforating wound of vein and subjacent tissues and anatomical structures.« less
Venous catheterization with ultrasound navigation
NASA Astrophysics Data System (ADS)
Kasatkin, A. A.; Urakov, A. L.; Nigmatullina, A. R.
2015-11-01
By ultrasound scanning it was determined that respiratory movements made by chest of healthy and sick person are accompanied by respiratory chest rise of internal jugular veins. During the exhalation of an individual diameter of his veins increases and during the breath it decreases down to the complete disappearing if their lumen. Change of the diameter of internal jugular veins in different phases can influence significantly the results of vein puncture and cauterization in patients. The purpose of this research is development of the method increasing the efficiency and safety of cannulation of internal jugular veins by the ultrasound visualization. We suggested the method of catheterization of internal jugular veins by the ultrasound navigation during the execution of which the puncture of venous wall by puncture needle and the following conduction of J-guide is carried out at the moment of patient's exhalation. This method decreases the risk of complications development during catheterization of internal jugular vein due to exclusion of perforating wound of vein and subjacent tissues and anatomical structures.
Techniques to Improve Ultrasound-Switchable Fluorescence Imaging
NASA Astrophysics Data System (ADS)
Kandukuri, Jayanth
Novel approaches to the improvement of ultrasound-switchable fluorescence (USF) imaging--a relatively new imaging modality that combines ultrasound and optical imaging techniques--have been proposed for early cancer detection. In USF, a high-intensity focused ultrasound (HIFU) beam is used to induce temperature rise within its acoustic focal region due to which a thermo-sensitive USF contrast agent undergoes a switch in its state by increasing the output of fluorescence photons. By using an increase in fluorescence, one can isolate and quantify the fluorescence properties within the ultrasonic focal area. Therefore, USF is able to provide fluorescence contrast while maintaining ultrasound resolution in tissue. The major challenge of the conventional USF technique is its low axial resolution and its sensitivity (i.e. its signal-to-noise ratio (SNR)). This work focuses on investigating and developing a novel USF system design that can improve the resolution and SNR of USF imaging for biological applications. This work can be divided into two major parts: characterizing the performance of a high-intensity focused ultrasound transducer; and improving the axial resolution and sensitivity of the USF technique. Preliminary investigation was conducted by using an IR camera setup to detect temperature variation and thereby study the performance of the high-intensity focused ultrasound transducer to quantify different parameters of ultrasound-induced temperature focal size (UTFS). Investigations are conducted for the purpose of high-resolution imaging with an emphasis on HIFU-induced thermal focus size, short duration of HIFU-induced temperature increase (to avoid thermal diffusion or conduction), and control of HIFU-induced temperature increase within a few degrees Celsius. Next, the focus was shifted to improving the sensitivity of the ultrasound-switchable fluorescence-imaging technique. In this study, the USF signal is encoded with the modulation frequency of the
Evaluation of targeting errors in ultrasound-assisted radiotherapy
Wang, Michael; Rohling, Robert; Duzenli, Cheryl; Clark, Brenda; Archip, Neculai
2014-01-01
A method for validating the start-to-end accuracy of a 3D ultrasound-based patient positioning system for radiotherapy is described. A radiosensitive polymer gel is used to record the actual dose delivered to a rigid phantom after being positioned using 3D ultrasound guidance. Comparison of the delivered dose with the treatment plan allows accuracy of the entire radiotherapy treatment process, from simulation to 3D ultrasound guidance, and finally delivery of radiation, to be evaluated. The 3D ultrasound patient positioning system has a number of features for achieving high accuracy and reducing operator dependence. These include using tracked 3D ultrasound scans of the target anatomy acquired using a dedicated 3D ultrasound probe during both the simulation and treatment sessions, automatic 3D ultrasound-to-ultrasound registration, and use of infra-red LED (IRED) markers of the optical position sensing system for registering simulation CT to ultrasound data. The mean target localization accuracy of this system was 2.5mm for four target locations inside the phantom, compared to 1.6mm obtained using the conventional patient positioning method of laser alignment. Since the phantom is rigid, this represents the best possible set-up accuracy of the system. Thus, these results suggest that 3D ultrasound-based target localization is practically feasible and potentially capable of increasing the accuracy of patient positioning for radiotherapy in sites where day-to-day organ shifts are greater than 1mm in magnitude. PMID:18723271
Theranostic Oxygen Delivery Using Ultrasound and Microbubbles
Kwan, James J.; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.
2012-01-01
Means to overcome tumor hypoxia have been the subject of clinical investigations since the 1960's; however these studies have yet to find a treatment which is widely accepted. It has been known for nearly a century that hypoxic cells are more resistant to radiotherapy than aerobic cells, and tumor hypoxia is a major factor leading to the resistance of tumors to radiation treatment as well as several cytotoxic agents. In this manuscript, the application of ultrasound combined with oxygen-carrier microbubbles is demonstrated as a method to locally increase dissolved oxygen. Microbubbles can also be imaged by ultrasound, thus providing the opportunity for image-guided oxygen delivery. Simulations of gas diffusion and microbubble gas exchange show that small amounts (down to 5 vol%) of a low-solubility osmotic gas can substantially increase microbubble persistence and therefore production rates and stability of oxygen-carrier microbubbles. Simulations also indicate that the lipid shell can be engineered with long-chain lipids to increase oxygen payload during in vivo transit. Experimental results demonstrate that the application of ultrasound to destroy the microbubbles significantly enhances the local oxygen release. We propose this technology as an application for ultrasound image-guided release of oxygen directly to hypoxic tissue, such as tumor sites to enhance radiotherapy. PMID:23382774
Mainiero, Martha B
2010-09-01
The status of axillary lymph nodes is a key prognostic indicator in patients with breast cancer and helps guide patient management. Sentinel lymph node biopsy is increasingly being used as a less morbid alternative to axillary lymph node dissection. However, when sentinel lymph node biopsy is positive, axillary dissection is typically performed for complete staging and local control. Axillary ultrasound and ultrasound-guided fine needle aspiration (USFNA) are useful for detecting axillary nodal metastasis preoperatively and can spare patients sentinel node biopsy, because those with positive cytology on USFNA can proceed directly to axillary dissection or neoadjuvant chemotherapy. Internal mammary nodes are not routinely evaluated, but when the appearance of these nodes is abnormal on imaging, further treatment or metastatic evaluation may be necessary. Copyright © 2010 Elsevier Inc. All rights reserved.
Transvaginal ultrasound-guided embryo transfer in IVF.
Larue, L; Keromnes, G; Massari, A; Roche, C; Moulin, J; Gronier, H; Bouret, D; Cassuto, N G; Ayel, J P
2017-05-01
To determine whether transvaginal ultrasound-guided embryo transfer is a technique that can be used routinely, whether it improves IVF outcomes and whether it makes difficult transfers easier and more successful. Non-randomized retrospective study conducted between 2012 and 2016 in the fertility center of the Diaconesses-Croix St-Simon hospital group. The outcomes of 3910 transfers, performed by 5 senior operators, under transabdominal ultrasound guidance are compared with those of 800 transfers, performed by 1 senior operator under transvaginal ultrasound guidance. The criteria studied are the feasibility of the technique and the percentage of pregnancies per transfer in the two populations described, as well as in the difficult and very difficult transfer populations. All the transfers were feasible under transvaginal ultrasound guidance without the use of forceps or additional instruments. The percentage of pregnancies per transfer is significantly increased, when the transfer is performed under transvaginal ultrasound guidance compared with that performed under transabdominal ultrasound guidance, in the general population (38%, n=800 vs 30%, n=3910; P 0.0004) and in the reference population characterized by age <38 years and >6 oocytes collected per puncture (45%, n=490 vs 36%, n=1968; P 0.002). The percentage of pregnancies per transfer (P/T) is not significantly different in the populations of easy transfers (n 695, 38% P/T), difficult transfers (n 58, 46% P/T; P=ns) and very difficult transfers (n 47, 34% P/T; P=ns). Embryo transfer is a key stage in IVF, in which the quality of performance determines the outcome. In this study, transvaginal ultrasound guidance of the transfer, which is the reference procedure in gynaecological imaging, significantly increases the percentage of pregnancies per transfer, both in the general population and in the reference population, compared with transfers performed under transabdominal ultrasound guidance. Transvaginal
Ultrasound elastography: principles, techniques, and clinical applications.
Dewall, Ryan J
2013-01-01
Ultrasound elastography is an emerging set of imaging modalities used to image tissue elasticity and are often referred to as virtual palpation. These techniques have proven effective in detecting and assessing many different pathologies, because tissue mechanical changes often correlate with tissue pathological changes. This article reviews the principles of ultrasound elastography, many of the ultrasound-based techniques, and popular clinical applications. Originally, elastography was a technique that imaged tissue strain by comparing pre- and postcompression ultrasound images. However, new techniques have been developed that use different excitation methods such as external vibration or acoustic radiation force. Some techniques track transient phenomena such as shear waves to quantitatively measure tissue elasticity. Clinical use of elastography is increasing, with applications including lesion detection and classification, fibrosis staging, treatment monitoring, vascular imaging, and musculoskeletal applications.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fang, Xu-Qian; Liu, Xiang-Fan; Yao, Ling
Highlights: •A novel FAK splicing mutation identified in breast tumor. •FAK-Del33 mutation promotes cell migration and invasion. •FAK-Del33 mutation regulates FAK/Src signal pathway. -- Abstract: Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introducedmore » into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.« less
Ribero, S; Podlipnik, S; Osella-Abate, S; Sportoletti-Baduel, E; Manubens, E; Barreiro, A; Caliendo, V; Chavez-Bourgeois, M; Carrera, C; Cassoni, P; Malvehy, J; Fierro, M T; Puig, S
2017-11-01
Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan-Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS). A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5-65.2) with a median follow-up time of 4.14 years (IQR 1.2-7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14-4.04) for skin metastases, 1.32 (IQR 0.57-3.29) for lymph node metastases and 2.84 (IQR 1.32-4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts. Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB-IIA. Copyright © 2017 Elsevier Ltd. All rights reserved.
Model for Porosity Changes Occurring during Ultrasound-Enhanced Transcorneal Drug Delivery.
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.
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.
Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou
2015-01-01
Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.
Influence of ultrasound pretreatment on wood physiochemical structure.
He, Zhengbin; Wang, Zhenyu; Zhao, Zijian; Yi, Songlin; Mu, Jun; Wang, Xiaoxu
2017-01-01
As an initial step to increase the use of renewable biomass resources, this study was aimed at investigating the effects of ultrasound pretreatment on structural changes of wood. Samples were pretreated by ultrasound with the power of 300W and frequency of 28kHz in aqueous soda solution, aqueous acetic acid, or distilled water, then pretreated and control samples were characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The results shown that ultrasound pretreatment is indeed effective in modifying the physiochemical structure of eucalyptus wood; the pretreatment decreased the quantity of alkali metals (e.g., potassium, calcium and magnesium) in the resulting material. Compared to the control group, the residual char content of samples pretreated in aqueous soda solution increased by 10.08%-20.12% and the reaction temperature decreased from 361°C to 341°C, however, in samples pretreated by ultrasound in acetic solution or distilled water, the residual char content decreased by 12.40%-21.45% and there were no significant differences in reactivity apart from a slightly higher maximum reaction rate. Ultrasound pretreatment increased the samples' crystallinity up to 35.5% and successfully removed cellulose, hemicellulose, and lignin from the samples; the pretreatment also increased the exposure of the sample to the treatment solutions, broke down sample pits, and generated collapses and microchannels on sample pits, and removed attachments in the samples. Copyright © 2016 Elsevier B.V. All rights reserved.
Marhofer, Peter; Fritsch, Gerhard
2015-01-01
Ultrasound is currently an important tool for diagnostic and interventional procedures. Ultrasound imaging provides significant advantages as compared to other imaging methods. The widespread use of ultrasound also carries the risk of drawbacks such as cross-infections. A large body of literature reports this possibly life-threatening side effect and specific patient populations are particularly at risk (e.g., neonates). Various methods of ultrasound probe disinfection are described; however, none of the mechanical or chemical probe disinfection procedures is optimal and, in particular, disinfection with high concentration of alcohol might be associated with ultrasound probe damage. The preparation of ultrasound probes with dedicated probe covers is a useful alternative for sterile working conditions. One ultrasound probe cover discussed in this paper is directly glued on to the ultrasound probe without the use of ultrasound coupling gel. By the use of sterile ultrasound coupling gel at the outer surface, additional effects on aseptic working conditions can be obtained.
Ultrasound Guidance and Monitoring of Laser-Based Fat Removal
Shah, Jignesh; Thomsen, Sharon; Milner, Thomas E.; Emelianov, Stanislav Y.
2009-01-01
Background and Objectives We report on a study to investigate feasibility of utilizing ultrasound imaging to guide laser removal of subcutaneous fat. Ultrasound imaging can be used to identify the tissue composition and to monitor the temperature increase in response to laser irradiation. Study Design/Materials and Methods Laser heating was performed on ex vivo porcine subcutaneous fat through the overlying skin using a continuous wave laser operating at 1,210 nm optical wavelength. Ultrasound images were recorded using a 10 MHz linear array-based ultrasound imaging system. Results Ultrasound imaging was utilized to differentiate between water-based and lipid-based regions within the porcine tissue and to identify the dermis-fat junction. Temperature maps during the laser exposure in the skin and fatty tissue layers were computed. Conclusions Results of our study demonstrate the potential of using ultrasound imaging to guide laser fat removal. PMID:19065554
Can Anatomists Teach Living Anatomy Using Ultrasound as a Teaching Tool?
ERIC Educational Resources Information Center
Jurjus, Rosalyn A.; Dimorier, Kathryn; Brown, Kirsten; Slaby, Frank; Shokoohi, Hamid; Boniface, Keith; Liu, Yiju Teresa
2014-01-01
The utilization of bedside ultrasound by an increasing number of medical specialties has created the need for more ultrasound exposure and teaching in medical school. Although there is a widespread support for more vertical integration of ultrasound teaching throughout the undergraduate curriculum, little is known about whether the quality of…
Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin
2017-06-15
Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. Copyright © 2017 Elsevier Inc. All rights reserved.
... page: //medlineplus.gov/ency/article/007646.htm Endoscopic ultrasound To use the sharing features on this page, please enable JavaScript. Endoscopic ultrasound is a type of imaging test. It is ...
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.
Tissue Bioeffects during Ultrasound-mediated Drug Delivery
NASA Astrophysics Data System (ADS)
Sutton, Jonathan
Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.
Zhang, J; Gao, Q; Zhou, Y; Dier, U; Hempel, N; Hochwald, S N
2016-04-14
Cancer cells often gains a growth advantage by taking up glucose at a high rate and undergoing aerobic glycolysis through intrinsic cellular factors that reprogram glucose metabolism. Focal adhesion kinase (FAK), a key transmitter of growth factor and anchorage stimulation, is aberrantly overexpressed or activated in most solid tumors, including pancreatic ductal adenocarcinomas (PDACs). We determined whether FAK can act as an intrinsic driver to promote aerobic glycolysis and tumorigenesis. FAK inhibition decreases and overexpression increases intracellular glucose levels during unfavorable conditions, including growth factor deficiency and cell detachment. Amplex glucose assay, fluorescence and carbon-13 tracing studies demonstrate that FAK promotes glucose consumption and glucose-to-lactate conversion. Extracellular flux analysis indicates that FAK enhances glycolysis and decreases mitochondrial respiration. FAK increases key glycolytic proteins, including enolase, pyruvate kinase M2 (PKM2), lactate dehydrogenase and monocarboxylate transporter. Furthermore, active/tyrosine-phosphorylated FAK directly binds to PKM2 and promotes PKM2-mediated glycolysis. On the other hand, FAK-decreased levels of mitochondrial complex I can result in reduced oxidative phosphorylation (OXPHOS). Attenuation of FAK-enhanced glycolysis re-sensitizes cancer cells to growth factor withdrawal, decreases cell viability and reduces growth of tumor xenografts. These observations, for the first time, establish a vital role of FAK in cancer glucose metabolism through alterations in the OXPHOS-to-glycolysis balance. Broadly targeting the common phenotype of aerobic glycolysis and more specifically FAK-reprogrammed glucose metabolism will disrupt the bioenergetic and biosynthetic supply for uncontrolled growth of tumors, particularly glycolytic PDAC.
Modulated Excitation Imaging System for Intravascular Ultrasound.
Qiu, Weibao; Wang, Xingying; Chen, Yan; Fu, Qiang; Su, Min; Zhang, Lining; Xia, Jingjing; Dai, Jiyan; Zhang, Yaonan; Zheng, Hairong
2017-08-01
Advances in methodologies and tools often lead to new insights into cardiovascular diseases. Intravascular ultrasound (IVUS) is a well-established diagnostic method that provides high-resolution images of the vessel wall and atherosclerotic plaques. High-frequency (>50 MHz) ultrasound enables the spatial resolution of IVUS to approach that of optical imaging methods. However, the penetration depth decreases when using higher imaging frequencies due to the greater acoustic attenuation. An imaging method that improves the penetration depth of high-resolution IVUS would, therefore, be of major clinical importance. Modulated excitation imaging is known to allow ultrasound waves to penetrate further. This paper presents an ultrasound system specifically for modulated-excitation-based IVUS imaging. The system incorporates a high-voltage waveform generator and an image processing board that are optimized for IVUS applications. In addition, a miniaturized ultrasound transducer has been constructed using a Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 single crystal to improve the ultrasound characteristics. The results show that the proposed system was able to provide increases of 86.7% in penetration depth and 9.6 dB in the signal-to-noise ratio for 60 MHz IVUS. In vitro tissue samples were also investigated to demonstrate the performance of the system.
American Institute of Ultrasound in Medicine
... Ultrasound Pediatric Ultrasound Point-of-Care Ultrasound Sonography Therapeutic Ultrasound Ultrasound in Global Health Ultrasound in Medical Education CME Center CME Tracker Annual Convention Journal Tests ...
[Novel dianostics and therapeutics with ultrasound technologies and nanotechnologies].
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.
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
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
CUQI: cardiac ultrasound video quality index
Razaak, Manzoor; Martini, Maria G.
2016-01-01
Abstract. Medical images and videos are now increasingly part of modern telecommunication applications, including telemedicinal applications, favored by advancements in video compression and communication technologies. Medical video quality evaluation is essential for modern applications since compression and transmission processes often compromise the video quality. Several state-of-the-art video quality metrics used for quality evaluation assess the perceptual quality of the video. For a medical video, assessing quality in terms of “diagnostic” value rather than “perceptual” quality is more important. We present a diagnostic-quality–oriented video quality metric for quality evaluation of cardiac ultrasound videos. Cardiac ultrasound videos are characterized by rapid repetitive cardiac motions and distinct structural information characteristics that are explored by the proposed metric. Cardiac ultrasound video quality index, the proposed metric, is a full reference metric and uses the motion and edge information of the cardiac ultrasound video to evaluate the video quality. The metric was evaluated for its performance in approximating the quality of cardiac ultrasound videos by testing its correlation with the subjective scores of medical experts. The results of our tests showed that the metric has high correlation with medical expert opinions and in several cases outperforms the state-of-the-art video quality metrics considered in our tests. PMID:27014715
Ultrasound-enhanced drug delivery for cancer.
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.
Power ultrasound in meat processing.
Alarcon-Rojo, A D; Janacua, H; Rodriguez, J C; Paniwnyk, L; Mason, T J
2015-09-01
Ultrasound has a wide range of applications in various agricultural sectors. In food processing, it is considered to be an emerging technology with the potential to speed up processes without damaging the quality of foodstuffs. Here we review the reports on the applications of ultrasound specifically with a view to its use in meat processing. Emphasis is placed on the effects on quality and technological properties such as texture, water retention, colour, curing, marinating, cooking yield, freezing, thawing and microbial inhibition. After the literature review it is concluded that ultrasound is a useful tool for the meat industry as it helps in tenderisation, accelerates maturation and mass transfer, reduces cooking energy, increases shelf life of meat without affecting other quality properties, improves functional properties of emulsified products, eases mould cleaning and improves the sterilisation of equipment surfaces. Copyright © 2015 Elsevier Ltd. All rights reserved.
Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.
Johns, Lennart D
2002-07-01
To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be
NASA Astrophysics Data System (ADS)
Makuta, T.; Tamakawa, Y.
2012-04-01
Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.
Neonatal Cranial Ultrasound: Are Current Safety Guidelines Appropriate?
Lalzad, Assema; Wong, Flora; Schneider, Michal
2017-03-01
Ultrasound can lead to thermal and mechanical effects in interrogated tissues. We reviewed the literature to explore the evidence on ultrasound heating on fetal and neonatal neural tissue. The results of animal studies have suggested that ultrasound exposure of the fetal or neonatal brain may lead to a significant temperature elevation at the bone-brain interface above current recommended safety thresholds. Temperature increases between 4.3 and 5.6°C have been recorded. Such temperature elevations can potentially affect neuronal structure and function and may also affect behavioral and cognitive function, such as memory and learning. However, the majority of these studies were carried out more than 25 y ago using non-diagnostic equipment with power outputs much lower than those of modern machines. New studies to address the safety issues of cranial ultrasound are imperative to provide current clinical guidelines and safety recommendations. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Ultrasound pretreatment for enhanced biogas production from olive mill wastewater.
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
Ultrasound in the evaluation of enthesitis: status and perspectives.
Gandjbakhch, Frédérique; Terslev, Lene; Joshua, Fredrick; Wakefield, Richard J; Naredo, Esperanza; D'Agostino, Maria Antonietta
2011-01-01
An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting enthesitis according to the OMERACT filter. Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of enthesitis, including describing features of enthesitis, were collected and metrological qualities of studies were assessed. After selection, 48 articles were analyzed. The definition of ultrasound enthesitis and elementary features varied among authors. Grey-scale enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%). Ultrasound has evidence to support face, content validity and reliability for the evaluation of enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of enthesitis in grey-scale and in Doppler for future applications.
Abid, Nadia; Ravier, Emmanuel; Promeyrat, Xavier; Codas, Ricardo; Fehri, Hakim Fassi; Crouzet, Sebastien; Martin, Xavier
2015-11-01
To compare fluoroscopy duration, radiation dose, and efficacy of two ultrasound stone localization systems during extracorporeal shockwave lithotripsy (SWL) treatment. Monocentric prospective data were obtained from patients consecutively treated for renal stones using the Sonolith(®) i-sys (EDAP TMS) lithotripter, with fluoroscopy combined with ultrasound localization using an "outline" Automatic Ultrasound Positioning Support (AUPS) (group A), or the "free-line" Visio-Track (VT) (EDAP-TMS) hand-held three-dimensional ultrasound stone locking system (group B). Efficacy rate was defined as the within-groups proportion stone free or with partial stone fragmentation not needing additional procedures. Statistical analysis used Pearson chi-square tests for categoric variables, nonparametric Mann-Whitney tests for continuous variables, and linear regression for operator learning curve with VT. Continuous variables were reported as median (range) values. Patients in group A (n=73) and group B (n=81) were comparable in baseline characteristics (age, kidney stone size, others) and in SWL application (duration, number of shocks, energy [Joules]). During SWL, the median (range) duration (seconds) of radiation exposure was 159.5 (0-690) in group A and 3.5 (0-478) in group B (P<0.001) and irradiation dose (mGy.cm(2)), 10598 (0-54843) in group A and 163 (0-13926) in group B (P<0.001). Fluoroscopy time significantly decreased with operator experience using VT. The efficacy rate was 54.5% in group A and 79.5% in group B (P=0.001). VT significantly reduced fluoroscopy use during SWL and the duration and dose of patient exposure to ionizing radiation. Stone treatment efficacy was significantly greater with VT mainly because of a better real-time monitoring of the stone.
Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.
Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum
2016-01-01
Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the
Anthropomorphic cardiac ultrasound phantom.
Smith, S W; Rinaldi, J E
1989-10-01
A new phantom is described which simulates the human cardiac anatomy for applications in ultrasound imaging, ultrasound Doppler, and color-flow Doppler imaging. The phantom consists of a polymer left ventricle which includes a prosthetic mitral and aortic valve and is connected to a mock circulatory loop. Aerated tap water serves as a blood simulating fluid and ultrasound contrast medium within the circulatory loop. The left ventricle is housed in a Lexan ultrasound visualization chamber which includes ultrasound viewing ports and acoustic absorbers. A piston pump connected to the visualization chamber by a single port pumps degassed water within the chamber which in turn pumps the left ventricle. Real-time ultrasound images and Doppler studies measure flow patterns through the valves and within the left ventricle.
Standardized ultrasound templates for diagnosing appendicitis reduce annual imaging costs.
Nordin, Andrew B; Sales, Stephen; Nielsen, Jason W; Adler, Brent; Bates, David Gregory; Kenney, Brian
2018-01-01
Ultrasound is preferred over computed tomography (CT) for diagnosing appendicitis in children to avoid undue radiation exposure. We previously reported our experience in instituting a standardized appendicitis ultrasound template, which decreased CT rates by 67.3%. In this analysis, we demonstrate the ongoing cost savings associated with using this template. Retrospective chart review for the time period preceding template implementation (June 2012-September 2012) was combined with prospective review through December 2015 for all patients in the emergency department receiving diagnostic imaging for appendicitis. The type of imaging was recorded, and imaging rates and ultrasound test statistics were calculated. Estimated annual imaging costs based on pretemplate ultrasound and CT utilization rates were compared with post-template annual costs to calculate annual and cumulative savings. In the pretemplate period, ultrasound and CT rates were 80.2% and 44.3%, respectively, resulting in a combined annual cost of $300,527.70. Similar calculations were performed for each succeeding year, accounting for changes in patient volume. Using pretemplate rates, our projected 2015 imaging cost was $371,402.86; however, our ultrasound rate had increased to 98.3%, whereas the CT rate declined to 9.6%, yielding an annual estimated cost of $224,853.00 and a savings of $146,549.86. Since implementation, annual savings have steadily increased for a cumulative cost savings of $336,683.83. Standardizing ultrasound reports for appendicitis not only reduces the use of CT scans and the associated radiation exposure but also decreases annual imaging costs despite increased numbers of imaging studies. Continued cost reduction may be possible by using diagnostic algorithms. Copyright © 2017 Elsevier Inc. All rights reserved.
Microalgae as feedstock for biodiesel production under ultrasound treatment - A review.
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 Assessment of Human Meniscus.
Viren, Tuomas; Honkanen, Juuso T; Danso, Elvis K; Rieppo, Lassi; Korhonen, Rami K; Töyräs, Juha
2017-09-01
The aim of the present study was to evaluate the applicability of ultrasound imaging to quantitative assessment of human meniscus in vitro. Meniscus samples (n = 26) were harvested from 13 knee joints of non-arthritic human cadavers. Subsequently, three locations (anterior, center and posterior) from each meniscus were imaged with two ultrasound transducers (frequencies 9 and 40 MHz), and quantitative ultrasound parameters were determined. Furthermore, partial-least-squares regression analysis was applied for ultrasound signal to determine the relations between ultrasound scattering and meniscus integrity. Significant correlations between measured and predicted meniscus compositions and mechanical properties were obtained (R 2 = 0.38-0.69, p < 0.05). The relationship between conventional ultrasound parameters and integrity of the meniscus was weaker. To conclude, ultrasound imaging exhibited a potential for evaluation of meniscus integrity. Higher ultrasound frequency combined with multivariate analysis of ultrasound backscattering was found to be the most sensitive for evaluation of meniscus integrity. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Watson, N J; Johal, R K; Glover, Z; Reinwald, Y; White, L J; Ghaemmaghami, A M; Morgan, S P; Rose, F R A J; Povey, M J W; Parker, N G
2013-12-01
The aim of this work is to demonstrate that the structural and fluidic properties of polymer foam tissue scaffolds, post-fabrication but prior to the introduction of cells, can be engineered via exposure to high power ultrasound. Our analysis is supported by measurements of fluid uptake during insonification and imaging of the scaffold microstructure via X-ray computed tomography, scanning electron microscopy and acoustic microscopy. The ultrasonic treatment is performed with a frequency of 30 kHz, average intensities up to 80,000 Wm(-2) and exposure times up to 20 h. The treatment is found to increase the mean pore size by over 10%. More striking is the improvement in fluid uptake: for scaffolds with only 40% water uptake via standard immersion techniques, we can routinely achieve full saturation of the scaffold over approximately one hour of exposure. These desirable modifications occur with negligible loss of scaffold integrity and mass, and are optimized when the ultrasound treatment is coupled to a pre-wetting stage with ethanol. Our findings suggest that high power ultrasound is highly targeted towards flow obstructions in the scaffold architecture, thereby providing an efficient means to promote pore interconnectivity and fluid transport in thick foam tissue scaffolds. © 2013.
Genomic damage induced by 1-MHz ultrasound in vitro.
Udroiu, Ion; Marinaccio, Jessica; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Sgura, Antonella
2018-01-01
Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Microbubble and ultrasound radioenhancement of bladder cancer
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
Ultrasound-enhanced delivery of antibiotics and anti-inflammatory drugs into the eye.
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.
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
Out of hospital point of care ultrasound: current use models and future directions.
Nelson, B P; Sanghvi, A
2016-04-01
Ultrasound has evolved from a modality that was once exclusively reserved to certain specialities of its current state, in which its portability and durability lend to its broadly increasing applications. This review describes portable ultrasound in the hospital setting and its comparison to gold standard imaging modalities. Also, this review summarizes current literature describing portable ultrasound use in prehospital, austere and remote environments, highlighting successes and barriers to use in these environments. Prehospital ultrasound has the ability to increase diagnostic ability and allow for therapeutic intervention in the field. In austere environments, ultrasound may be the only available imaging modality and thus can guide diagnosis, therapeutics and determine which patients may need emergent transfer to a healthcare facility. The most cutting edge applications of portable ultrasound employ telemedicine to obtain and transmit ultrasound images. This technology and ability to transmit images via satellite and cellular transmission can allow for even novice users to obtain interpretable images in austere environments. Portable ultrasound uses have steadily grown and will continue to do so with the introduction of more portable and durable technologies. As applications continue to grow, certain technologic considerations and future directions are explored.
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.
Minkis, Kira; Alam, Murad
2014-01-01
Ultrasound skin tightening is a noninvasive, nonablative method that allows for energy deposition into the deep dermal and subcutaneous tissue while avoiding epidermal heating. Ultrasound coagulation is confined to arrays of 1-mm(3) zones that include the superficial musculoaponeurotic system and connective tissue. This technology gained approval from the Food and Drug Administration as the first energy-based skin "lifting" device, specifically for lifting lax tissue on the neck, submentum, and eyebrows. Ultrasound has the unique advantage of direct visualization of treated structures during treatment. Ultrasound is a safe and efficacious treatment for mild skin tightening and lifting. Copyright © 2014 Elsevier Inc. All rights reserved.
Ultrasound: Bladder (For Parents)
... the computer screen. A technician (sonographer) trained in ultrasound imaging will spread a clear, warm gel on the ... specially trained in reading and interpreting X-ray, ultrasound, and other imaging studies) will interpret the ultrasound results and then ...
Ultrasound: Pelvis (For Parents)
... the computer screen. A technician (sonographer) trained in ultrasound imaging will spread a clear, warm gel on the ... specially trained in reading and interpreting X-ray, ultrasound, and other imaging studies) will interpret the ultrasound results and then ...
Ultrasound in regional anaesthesia.
Griffin, J; Nicholls, B
2010-04-01
Ultrasound guidance is rapidly becoming the gold standard for regional anaesthesia. There is an ever growing weight of evidence, matched with improving technology, to show that the use of ultrasound has significant benefits over conventional techniques, such as nerve stimulation and loss of resistance. The improved safety and efficacy that ultrasound brings to regional anaesthesia will help promote its use and realise the benefits that regional anaesthesia has over general anaesthesia, such as decreased morbidity and mortality, superior postoperative analgesia, cost-effectiveness, decreased postoperative complications and an improved postoperative course. In this review we consider the evidence behind the improved safety and efficacy of ultrasound-guided regional anaesthesia, before discussing its use in pain medicine, paediatrics and in the facilitation of neuraxial blockade. The Achilles' heel of ultrasound-guided regional anaesthesia is that anaesthetists are far more familiar with providing general anaesthesia, which in most cases requires skills that are achieved faster and more reliably. To this ends we go on to provide practical advice on ultrasound-guided techniques and the introduction of ultrasound into a department.
Frequency Dependence of Ultrasound Neurostimulation in the Mouse Brain
Ye, Patrick Peiyong; Brown, Julian R.; Pauly, Kim Butts
2016-01-01
Ultrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies less than 1 MHz, with a trend towards improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution. We investigate the ultrasound neuromodulation effects in mice at various frequencies both below and above 1 MHz and find that frequencies up to 2.9 MHz can still be effective for generating motor responses, but also confirm that as frequency increases, sonications require significantly more intensity to achieve equivalent efficacy. We argue that our results provide evidence that favors either a particle displacement or a cavitation-based mechanism for the phenomenon of ultrasound neuromodulation. PMID:27090861
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.
Interactive multimedia for prenatal ultrasound training.
Lee, W; Ault, H; Kirk, J S; Comstock, C H
1995-01-01
This demonstration project examines the utility of interactive multimedia for prenatal ultrasound training. A laser-disc library was linked to a three-dimensional (3-D) heart model and other computer-based training materials through interactive multimedia. A testing module presented ultrasound anomalies and related questions to house-staff physicians through the image library. Users were asked to evaluate these training materials on the basis of perceived instructional value, question content, subjects covered, graphics interface, and ease of use; users were also asked for their comments. House-staff physicians indicated that they consider interactive multimedia to be a helpful adjunct to their core fetal imaging rotation. During a 9-month period, 16 house-staff physicians correctly diagnosed 78 +/- 4% of unknown cases presented through the testing module. The 3-D heart model was also perceived to be a useful teaching aid for spatial orientation skills. Our findings suggest that interactive multimedia and volume visualization models can be used to supplement traditional prenatal ultrasound training. The system provides a broad exposure to ultrasound anomalies, increases opportunities for postnatal correlation, emphasizes motion video for ultrasound training, encourages development of independent diagnostic ability, and helps physicians understand anatomic orientation. We hypothesize that interactive multimedia-based tutorials provide a better overall training experience for house-staff physicians. However, these supplementary methods will require formal evaluation of effectiveness to better understand their potential educational impact.
Leighton, Timothy G
2007-01-01
This paper is based on material presented at the start of a Health Protection Agency meeting on ultrasound and infrasound. In answering the question 'what is ultrasound?', it shows that the simple description of a wave which transports mechanical energy through the local vibration of particles at frequencies of 20 kHz or more, with no net transport of the particles themselves, can in every respect be misleading or even incorrect. To explain the complexities responsible for this, the description of ultrasound is first built up from the fundamental properties of these local particle vibrations. This progresses through an exposition of the characteristics of linear waves, in order to explain the propensity for, and properties of, the nonlinear propagation which occurs in many practical ultrasonic fields. Given the Health Protection environment which framed the original presentation, explanation and examples are given of how these complexities affect issues of practical importance. These issues include the measurement and description of fields and exposures, and the ability of ultrasound to affect tissue (through microstreaming, streaming, cavitation, heating, etc.). It is noted that there are two very distinct regimes, in terms of wave characteristics and potential for bioeffect. The first concerns the use of ultrasound in liquids/solids, for measurement or material processing. For biomedical applications (where these two processes are termed diagnosis and therapy, respectively), the issue of hazard has been studied in depth, although this has not been done to such a degree for industrial uses of ultrasound in liquids/solids (sonar, non-destructive testing, ultrasonic processing etc.). However, in the second regime, that of the use of ultrasound in air, although the waves in question tend to be of much lower intensities than those used in liquids/solids, there is a greater mismatch between the extent to which hazard has been studied, and the growth in commercial
Lai, Chun-Yen; Kruse, Dustin E.; Ferrara, Katherine W.; Caskey, Charles F.
2014-01-01
Ultrasound thermometry provides noninvasive two-dimensional (2-D) temperature monitoring, and in this paper, we have investigated the use of computed tomography (CT) radiodensity to characterize tissues to improve the accuracy of ultrasound thermometry. Agarose-based tissue-mimicking phantoms were created with glyceryl trioleate (a fat-mimicking material) concentration of 0, 10, 20, 30, 40, and 50%. The speed of sound (SOS) of the phantoms was measured over a temperature range of 22.1–41.1°C. CT images of the phantoms were acquired by a clinical dedicated breast CT scanner, followed by calculation of the Hounsfield units (HU). The phantom was heated with a therapeutic acoustic pulse (1.54 MHz), while RF data were acquired with a 10-MHz linear-array transducer. 2-D speckle tracking was used to calculate the thermal strain offline. The tissue dependent thermal strain parameter required for ultrasound thermometry was analyzed and correlated with CT radiodensity, followed by validation of the temperature prediction. Results showed that the change in SOS with the temperature increase was opposite in sign between the 0–10% and 20–50% trioleate phantoms. The inverse of the tissue dependent thermal strain parameter of the phantoms was correlated with the CT radiodensity (R2 = 0.99). A blinded ultrasound thermometry study on phantoms with a trioleate range of 5–35% demonstrated the capability to estimate the tissue dependent thermal strain parameter and estimate temperature with error less than ~1°C. In conclusion, CT radiodensity may provide a method for improving ultrasound thermometry in heterogeneous tissues. PMID:24107918
Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel
2009-11-01
Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.
Dinh, Vi Am; Frederick, Jon; Bartos, Rebekah; Shankel, Tamara M; Werner, Leonard
2015-01-01
Increasing emphasis has been placed on point-of-care ultrasound in medical school. The overall effects of ultrasound curriculum implementation on the traditional physical examination skills of medical students are still unknown. We studied the effects on the Objective Standardized Clinical Examination (OSCE) scores of year 1 medical students before and after ultrasound curriculum implementation. An ultrasound curriculum was incorporated into the physical diagnosis course for year 1 medical students in the 2012-2013 academic year. We performed a prospective observational study comparing traditional OSCE scores of year 1 medical students exposed to the ultrasound curriculum (post-ultrasound) versus historic year 1 medical student controls (pre-ultrasound) with no ultrasound exposure. Questionnaire data were also obtained from year 1 medical students and physical diagnosis faculty to assess attitudes toward ultrasound implementation. The final overall OSCE scores were graded with a 5-point Likert-type scale from unsatisfactory to outstanding. There was a significant increase in outstanding scores in the post-ultrasound compared to the pre-ultrasound group (27.0% versus 10.9%; P< .001). The post-ultrasound group had significantly (P< .05) increased first-time pass rates on blood pressure measurements, the abdominal examination, and professionalism. Student and physical diagnosis faculty questionnaire data showed an overall positive response, with most agreeing or strongly agreeing that ultrasound should be included in the future year 1 medical student curriculum. Ultrasound implementation into a physical diagnosis curriculum for year 1 medical students is feasible and may improve their overall traditional physical examination skills. © 2015 by the American Institute of Ultrasound in Medicine.
Bernard, Stewart; Richardson, Clare; Hamann, Carsten R; Lee, Steve; Dinh, Vi Am
2015-08-01
With the increased implementation of ultrasound in medical education, it is important to continually improve instructional methods. In this study, we demonstrate that by augmenting the traditional methods of instructor demonstration and student practice on a healthy volunteer with additional modalities, such as didactic presentation, simulated pathologic cases, and simulated procedures, students gain a more comprehensive understanding of and confidence in ultrasound technique and pathology. A multimodal curriculum was developed and applied to head and neck ultrasound sessions of our institution's Ultrasound Symposium. Participants were asked to fill out surveys rating each instructional modality as well as preinstructional and postinstructional confidence. The survey results were divided into a group of first- and second-year medical students who had previous ultrasound training and a group of third- and fourth-year students who were ultrasound "naïve." The survey showed that the first- and second-year student group (n = 8) had an average preinstructional confidence of 4.14/10 compared to 1.44/10 in the third- and fourth-year student group (n = 9) (P = .003). Following the instructional sessions, the students' confidence increased respectively to 8.14/10 and 7.78/10 (P= .53), showing a 4.00 (96%) increase in the first- and second-year group and a 6.34 (440%) increase in the third- and fourth-year group. The combined results of all student teaching modality ratings showed that instructor demonstration was rated the highest (9.47) and computerized simulation lowest (8.25). Overall, our study shows that multimodal ultrasound instruction was beneficial in increasing both ultrasound-trained and ultrasound-naïve medical students' confidence in head and neck ultrasound. © 2015 by the American Institute of Ultrasound in Medicine.
NASA Astrophysics Data System (ADS)
Mehrmohammadi, Mohammad; Ma, Li L.; Chen, Yun-Sheng; Qu, Min; Joshi, Pratixa; Chen, Raeanna M.; Johnston, Keith P.; Emelianov, Stanislav
2010-02-01
Photothermal therapy is a laser-based non-invasive technique for cancer treatment. Photothermal therapy can be enhanced by employing metal nanoparticles that absorb the radiant energy from the laser leading to localized thermal damages. Targeting of nanoparticles leads to more efficient uptake and localization of photoabsorbers thus increasing the effectiveness of the treatment. Moreover, efficient targeting can reduce the required dosage of photoabsorbers; thereby reducing the side effects associated with general systematic administration of nanoparticles. Magnetic nanoparticles, due to their small size and response to an external magnetic field gradient have been proposed for targeted drug delivery. In this study, we investigate the applicability of multifunctional nanoparticles (e.g., magneto-plasmonic nanoparticles) and magneto-motive ultrasound imaging for image-guided photothermal therapy. Magneto-motive ultrasound imaging is an ultrasound based imaging technique capable of detecting magnetic nanoparticles indirectly by utilizing a high strength magnetic field to induce motion within the magnetically labeled tissue. The ultrasound imaging is used to detect the internal tissue motion. Due to presence of the magnetic component, the proposed multifunctional nanoparticles along with magneto-motive ultrasound imaging can be used to detect the presence of the photo absorbers. Clearly the higher concentration of magnetic carriers leads to a monotonic increase in magneto-motive ultrasound signal. Thus, magnetomotive ultrasound can determine the presence of the hybrid agents and provide information about their location and concentration. Furthermore, the magneto-motive ultrasound signal can indicate the change in tissue elasticity - a parameter that is expected to change significantly during the photothermal therapy. Therefore, a comprehensive guidance and assessment of the photothermal therapy may be feasible through magneto-motive ultrasound imaging and
Calibration and Evaluation of Ultrasound Thermography using Infrared Imaging
Hsiao, Yi-Sing; Deng, Cheri X.
2015-01-01
Real-time monitoring of the spatiotemporal evolution of tissue temperature is important to ensure safe and effective treatment in thermal therapies including hyperthermia and thermal ablation. Ultrasound thermography has been proposed as a non-invasive technique for temperature measurement, and accurate calibration of the temperature-dependent ultrasound signal changes against temperature is required. Here we report a method that uses infrared (IR) thermography for calibration and validation of ultrasound thermography. Using phantoms and cardiac tissue specimens subjected to high-intensity focused ultrasound (HIFU) heating, we simultaneously acquired ultrasound and IR imaging data from the same surface plane of a sample. The commonly used echo time shift-based method was chosen to compute ultrasound thermometry. We first correlated the ultrasound echo time shifts with IR-measured temperatures for material-dependent calibration and found that the calibration coefficient was positive for fat-mimicking phantom (1.49 ± 0.27) but negative for tissue-mimicking phantom (− 0.59 ± 0.08) and cardiac tissue (− 0.69 ± 0.18 °C-mm/ns). We then obtained the estimation error of the ultrasound thermometry by comparing against the IR measured temperature and revealed that the error increased with decreased size of the heated region. Consistent with previous findings, the echo time shifts were no longer linearly dependent on temperature beyond 45 – 50 °C in cardiac tissues. Unlike previous studies where thermocouples or water-bath techniques were used to evaluate the performance of ultrasound thermography, our results show that high resolution IR thermography provides a useful tool that can be applied to evaluate and understand the limitations of ultrasound thermography methods. PMID:26547634
Grewal, Jagteshwar; Zhang, Jun; Mikolajczyk, Rafael T; Ford, Jessie
2010-08-01
Estimates of gestational age based on early second-trimester ultrasound often differ from that based on the last menstrual period (LMP) even when a woman is certain about her LMP. Discrepancies in these gestational age estimates may be associated with an increased risk of cesarean section and low birth weight. We analyzed 7228 singleton, low-risk, white women from The Routine Antenatal Diagnostic Imaging with Ultrasound trial. The women were recruited at less than 14 weeks of gestation and received ultrasound exams between 15 and 22 weeks. Our results indicate that among nulliparous women, the risk of cesarean section increased from 10% when the ultrasound-based gestational age exceeded the LMP-based estimate by 4 days to 60% when the discrepancy increased to 21 days. Moreover, for each additional day the ultrasound-based estimate exceeded the LMP-based estimate, birth weight was higher by 9.6 g. Our findings indicate that a positive discrepancy (i.e., ultrasound-based estimate exceeds LMP-based estimate) in gestational age is associated with an increased risk of cesarean section. A negative discrepancy, by contrast, may reflect early intrauterine growth restriction and an increased risk of low birth weight. Copyright Thieme Medical Publishers.
Stock, Konrad Friedrich; Klein, Bettina; Steubl, Dominik; Lersch, Christian; Heemann, Uwe; Wagenpfeil, Stefan; Eyer, Florian; Clevert, Dir-Andre
2015-10-01
Time savings and clinical accuracy of a new miniature ultrasound device was investigated utilizing comparison with conventional high-end ultrasound instruments. Our objective was to determine appropriate usage and limitations of this diagnostic tool in internal medicine. We investigated 28 patients from the internal-medicine department. Patients were examined with the Acuson P10 portable device and a Sonoline Antares instrument in a cross-over design. All investigations were carried out at the bedside; the results were entered on a standardized report form. The time for the ultrasound examination (transfer time, setting up and disassembly, switching on and off, and complete investigation time) was recorded separately. Mean time for overall examination per patient with the portable ultrasound device was shorter (25.0 ± 4.5 min) than with the high-end machine (29.4 ± 4.4 min; p < 0.001). When measuring the size of liver, spleen, and kidneys, the values obtained differed significantly between portable device and the high-end instrument. In our study, we identified 113 pathological ultrasound findings with the high-end ultrasound machine, while 82 pathological findings (73%) were concordantly detected with the portable ultrasound device. The main diagnostic strengths of the portable device were in the detection of ascites (sensitivity 80%), diagnosis of fatty liver, and identification of severe parenchymal liver damage. The clinical utility of portable ultrasound machines is limited. There will be clinical roles for distinct clinical questions such as detection of ascites or pleural effusion when used by experienced examiners. However, sensitivity in detecting multiple pathologies is not comparable to high-end ultrasound machines.
High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems.
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.
Ultrasound Imaging System Video
NASA Technical Reports Server (NTRS)
2002-01-01
In this video, astronaut Peggy Whitson uses the Human Research Facility (HRF) Ultrasound Imaging System in the Destiny Laboratory of the International Space Station (ISS) to image her own heart. The Ultrasound Imaging System provides three-dimension image enlargement of the heart and other organs, muscles, and blood vessels. It is capable of high resolution imaging in a wide range of applications, both research and diagnostic, such as Echocardiography (ultrasound of the heart), abdominal, vascular, gynecological, muscle, tendon, and transcranial ultrasound.
Clinical diagnosis by transcutaneous Doppler ultrasound
Wyse, R. K. H.
1982-01-01
Transcutaneous Doppler ultrasound represents a convenient, reliable technique for the non-invasive diagnosis and assessment of a rapidly increasing number of diverse circulatory disorders. ImagesFig. 2Fig. 3 PMID:7050948
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.
[Ultrasound findings in rhabdomyolysis].
Carrillo-Esper, Raúl; Galván-Talamantes, Yazmin; Meza-Ayala, Cynthia Margarita; Cruz-Santana, Julio Alberto; Bonilla-Reséndiz, Luis Ignacio
Rhabdomyolysis is defined as skeletal muscle necrosis. Ultrasound assessment has recently become a useful tool for the diagnosis and monitoring of muscle diseases, including rhabdomyolysis. A case is presented on the ultrasound findings in a patient with rhabdomyolysis. To highlight the importance of ultrasound as an essential part in the diagnosis in rhabdomyolysis, to describe the ultrasound findings, and review the literature. A 30 year-old with post-traumatic rhabdomyolysis of both thighs. Ultrasound was performed using a Philips Sparq model with a high-frequency linear transducer (5-10MHz), in low-dimensional scanning mode (2D), in longitudinal and transverse sections at the level of both thighs. The images obtained showed disorganisation of the orientation of the muscle fibres, ground glass image, thickening of the muscular fascia, and the presence of anechoic areas. Ultrasound is a useful tool in the evaluation of rhabdomyolysis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Gao, Ning; He, Huimin; Xiao, Li; Gao, Xiaojie; Shi, Hongyan; Wu, Qiong; Xu, Nan; Lei, Yuqing; Song, Xigui; Hou, Yingchun
2015-04-01
Focal adhesion kinase (FAK) plays important roles in cancer development. However, the significance of FAK expression in colorectal carcinoma and hepatocellular carcinoma has not been clarified. This study aims to explore the roles FAK played in the progression of colorectal carcinoma and hepatocellular carcinoma. RNAi method was used to inhibit the expression of FAK in Caco2 and SMMC-7721 cells. Reverse transcriptase polymerase chain reaction analysis and Western blot analysis were used to examine mRNA and protein expression of FAK. Then, the proliferation, motility and apoptosis of both types of cells were detected using MTT assay, wound healing/transwell assay and nuclear staining assay. The microstructure changes (F-actin, β-tubulin and lamin B1) of SMMC-7721 cells were visualized by immunofluorescence. FAK was overexpressed in both cell lines and down-regulation of FAK resulted in suppression of cell proliferation, inhibition of cell migration and invasion. The apoptosis of cells was increased significantly following the FAK expression inhibition. Moreover, actin polymerization, β-tubulin and lamin B1 expression of cells were significantly decreased. The results highlight the role of FAK in the progression of cancers. These findings suggest FAK serve as a potential therapeutic target for cancer therapy.
MO-AB-210-03: Workshop [Advancements in high intensity focused ultrasound
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lu, Z.
The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant
MO-AB-210-02: Ultrasound Imaging and Therapy-Hands On Workshop
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sammet, S.
The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant
MO-AB-210-01: Ultrasound Imaging and Therapy-Hands On Workshop
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lu, Z.
The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant
ERIC Educational Resources Information Center
Hughes, Stephen
2001-01-01
Explains the basic principles of ultrasound using everyday physics. Topics include the generation of ultrasound, basic interactions with material, and the measurement of blood flow using the Doppler effect. (Author/MM)
Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects
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
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.
Using Ultrasound to Enhance Medical Students' Femoral Vascular Physical Examination Skills.
Ahn, Justin S; French, Andrew J; Thiessen, Molly E W; Browne, Vaughn; Deutchman, Mark; Guiton, Gretchen; Madigosky, Wendy; Kendall, John L
2015-10-01
To determine whether the addition of ultrasound to traditional physical examination instruction improves junior medical students' abilities to locate the femoral pulse. Initially, 150 second-year medical students were taught the femoral pulse examination using traditional bedside teaching on standardized patients and online didactic videos. Students were then randomized into 2 groups: group 1 received ultrasound training first and then completed the standardized examination; and group 2 performed the standardized examination first and then received ultrasound training. On the standardized patients, the femoral artery was marked with invisible ink before the sessions using ultrasound. Compared to these markers, students were then evaluated on the accuracy of femoral artery pulse palpation and the estimated location of the femoral vein. All students completed a self-assessment survey after the ultrasound sessions. Ultrasound training improved the students' ability to palpate the femoral pulse (P= .02). However, ultrasound did not facilitate correct estimation of the femoral vein's anatomic location (P = .09). Confidence levels in localizing the femoral artery and vein were equal between groups at baseline, and both increased after the ultrasound sessions. The addition of ultrasound teaching to traditional physical examination instruction enhanced medical student competency and confidence with the femoral vascular examination. However, understanding of anatomy may require emphasis on precourse didactic material, but further study is required. © 2015 by the American Institute of Ultrasound in Medicine.
Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents
Zhang, Qimei; Morgan, Stephen P.; O’Shea, Paul; Mather, Melissa L.
2016-01-01
A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the “wagging” of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes. PMID:27467748
Focused Ultrasound Surgery for Uterine Fibroids
... ultrasound surgery, your doctor may perform a pelvic magnetic resonance imaging (MRI) scan before treatment. Focused ultrasound surgery — also called magnetic resonance-guided focused ultrasound surgery or focused ultrasound ...
Yan, X; Zhao, C; Tian, C; Wen, S; He, X; Zhou, Y
2017-08-01
To explore HIFU treatment for uterine arteriovenous malformation. A case report. Gynaecological department in a university teaching hospital of China. A patient with uterine arteriovenous malformation. The diagnosis of uterine arteriovenous malformation was made through MRI. Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation was performed. HIFU is effective in treating uterine arteriovenous malformation. The patient had reduction of the lesion volume and obvious symptom relief, without significant adverse effects. HIFU can be used as a new treatment option for uterine arteriovenous malformation. Ultrasound-guided high-intensity focused ultrasound ablation is effective in treating uterine arteriovenous malformation. © 2017 Royal College of Obstetricians and Gynaecologists.
New heights in ultrasound: first report of spinal ultrasound from the international space station.
Marshburn, Thomas H; Hadfield, Chris A; Sargsyan, Ashot E; Garcia, Kathleen; Ebert, Douglas; Dulchavsky, Scott A
2014-01-01
Changes in the lumbar and sacral spine occur with exposure to microgravity in astronauts; monitoring these alterations without radiographic capabilities on the International Space Station (ISS) requires novel diagnostic solutions to be developed. We evaluated the ability of point-of-care ultrasound, performed by nonexpert-operator astronauts, to provide accurate anatomic information about the spine in long-duration crewmembers in space. Astronauts received brief ultrasound instruction on the ground and performed in-flight cervical and lumbosacral ultrasound examinations using just-in-time training and remote expert tele-ultrasound guidance. Ultrasound examinations on the ISS used a portable ultrasound device with real-time communication/guidance with ground experts in Mission Control. The crewmembers were able to obtain diagnostic-quality examinations of the cervical and lumbar spine that would provide essential information about acute or chronic changes to the spine. Spinal ultrasound provides essential anatomic information in the cervical and lumbosacral spine; this technique may be extensible to point-of-care situations in emergency departments or resource-challenged areas without direct access to additional radiologic capabilities. Copyright © 2014 Elsevier Inc. All rights reserved.
Assessment of a Low-Cost Ultrasound Pericardiocentesis Model
Campo dell'Orto, Marco; Hempel, Dorothea; Starzetz, Agnieszka; Seibel, Armin; Hannemann, Ulf; Walcher, Felix; Breitkreutz, Raoul
2013-01-01
Introduction. The use of ultrasound during resuscitation is emphasized in the latest European resuscitation council guidelines of 2013 to identify treatable conditions such as pericardial tamponade. The recommended standard treatment of tamponade in various guidelines is pericardiocentesis. As ultrasound guidance lowers the complication rates and increases the patient's safety, pericardiocentesis should be performed under ultrasound guidance. Acute care physicians actually need to train emergency pericardiocentesis. Methods. We describe in detail a pericardiocentesis ultrasound model, using materials at a cost of about 60 euros. During training courses of focused echocardiography n = 67, participants tested the phantom and completed a 16-item questionnaire, assessing the model using a visual analogue scale (VAS). Results. Eleven of fourteen questions were answered with a mean VAS score higher than 60% and thus regarded as showing the strengths of the model. Unrealistically outer appearance and heart shape were rated as weakness of the model. A total mean VAS score of all questions of 63% showed that participants gained confidence for further interventions. Conclusions. Our low-cost pericardiocentesis model, which can be easily constructed, may serve as an effective training tool of ultrasound-guided pericardiocentesis for acute and critical care physicians. PMID:24288616
Cranial Ultrasound/Head Ultrasound
... the patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... by a computer, which in turn creates a real-time picture on the monitor. One or more frames ...
Clemente, Carolina F M Z; Tornatore, Thais F; Theizen, Thais H; Deckmann, Ana C; Pereira, Tiago C; Lopes-Cendes, Iscia; Souza, José Roberto M; Franchini, Kleber G
2007-12-07
Hypertrophy is a critical event in the onset of failure in chronically overloaded hearts. Focal adhesion kinase (FAK) has attracted particular attention as a mediator of hypertrophy induced by increased load. Here, we demonstrate increased expression and phosphorylation of FAK in the hypertrophic left ventricles (LVs) of aortic-banded mice. We used an RNA interference strategy to examine whether FAK signaling plays a role in the pathophysiology of load-induced LV hypertrophy and failure. Intrajugular delivery of specific small interfering RNA induced prolonged FAK silencing ( approximately 70%) in both normal and hypertrophic LVs. Myocardial FAK silencing was accompanied by prevention, as well as reversal, of load-induced left ventricular hypertrophy. The function of LVs was preserved and the survival rate was higher in banded mice treated with small interfering RNA targeted to FAK, despite the persistent pressure overload. Studies in cardiac myocytes and fibroblasts harvested from LVs confirmed the ability of the systemically administered specific small interfering RNA to silence FAK in both cell types. Further analysis indicated attenuation of cardiac myocyte hypertrophic growth and of the rise in the expression of beta-myosin heavy chain in overloaded LVs. Moreover, FAK silencing was demonstrated to attenuate the rise in the fibrosis, collagen content, and activity of matrix metalloproteinase-2 in overloaded LVs, as well as the rise of matrix metalloproteinase-2 protein expression in fibroblasts harvested from overloaded LVs. This study provides novel evidence that FAK may be involved in multiple aspects of the pathophysiology of cardiac hypertrophy and failure induced by pressure overload.
Ultrasound-Enhanced Delivery of Antibiotics and Anti-Inflammatory Drugs into the Eye
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
Transvaginal ultrasound (image)
Transvaginal ultrasound is a method of imaging the genital tract in females. A hand held probe is inserted directly ... vaginal cavity to scan the pelvic structures, while ultrasound pictures are viewed on a monitor. The test ...
Abdominal ultrasound is a scanning technique used to image the interior of the abdomen. Like the X-ray, MRI, ... it has its place as a diagnostic tool. Ultrasound scans use high frequency sound waves to produce ...
Ultrasound-assisted extraction of rare-earth elements from carbonatite rocks.
Diehl, Lisarb O; Gatiboni, Thais L; Mello, Paola A; Muller, Edson I; Duarte, Fabio A; Flores, Erico M M
2018-01-01
In view of the increasing demand for rare-earth elements (REE) in many areas of high technology, alternative methods for the extraction of these elements have been developed. In this work, a process based on the use of ultrasound for the extraction of REE from carbonatite (an igneous rock) is proposed to avoid the use of concentrated reagents, high temperature and excessive extraction time. In this pioneer work for REE extraction from carbonatite rocks in a preliminary investigation, ultrasonic baths, cup horn systems or ultrasound probes operating at different frequencies and power were evaluated. In addition, the power released to the extraction medium and the ultrasound amplitude were also investigated and the temperature and carbonatite mass/volume of extraction solution ratio were optimized to 70°C and 20mg/mL, respectively. Better extraction efficiencies (82%) were obtained employing an ultrasound probe operating at 20kHz for 15min, ultrasound amplitude of 40% (692Wdm -3 ) and using a diluted extraction solution (3% v/v HNO 3 +2% v/v HCl). It is important to mention that high extraction efficiency was obtained even using a diluted acid mixture and relatively low temperature in comparison to conventional extraction methods for REE. A comparison of results with those obtained by mechanical stirring (500rpm) using the same conditions (time, temperature and extraction solution) was carried out, showing that the use of ultrasound increased the extraction efficiency up to 35%. Therefore, the proposed ultrasound-assisted procedure can be considered as a suitable alternative for high efficiency extraction of REE from carbonatite rocks. Copyright © 2017 Elsevier B.V. All rights reserved.
Microbubbles in Ultrasound-Triggered Drug and Gene Delivery
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
Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.
Wang, Chung-Hsin; Kang, Shih-Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu-Fen; Yeh, Chih-Kuang
2012-02-01
Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability. Copyright © 2011 Elsevier Ltd. All rights reserved.
Segura-Grau, A; Sáez-Fernández, A; Rodríguez-Lorenzo, A; Díaz-Rodríguez, N
2014-01-01
Ultrasound is a non-invasive, accessible, and versatile diagnostic technique that uses high frequency ultrasound waves to define outline the organs of the human body, with no ionising radiation, in real time and with the capacity to visual several planes. The high diagnostic yield of the technique, together with its ease of uses plus the previously mentioned characteristics, has currently made it a routine method in daily medical practice. It is for this reason that the multidisciplinary character of this technique is being strengthened every day. To be able to perform the technique correctly requires knowledge of the physical basis of ultrasound, the method and the equipment, as well as of the human anatomy, in order to have the maximum information possible to avoid diagnostic errors due to poor interpretation or lack of information. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Belcik, J. Todd; Davidson, Brian P.; Xie, Aris; Wu, Melinda D.; Yadava, Mrinal; Qi, Yue; Liang, Sherry; Chon, Chae Ryung; Ammi, Azzdine Y.; Field, Joshua; Harmann, Leanne; Chilian, William M.; Linden, Joel; Lindner, Jonathan R.
2017-01-01
Background Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signalling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. Methods Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for ten minutes after intravenous injection of 2×108 lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signalling pathways were assessed by studying interventions that either (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or KATP channels; or (3) inhibited downstream signalling pathways involving endothelial nitric oxide synthase (eNOS) or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease (SCD). Results Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hrs in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with SCD. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced a nearly 40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or through adenosine produced by ectonucleotidase activity. Combined
Belcik, J Todd; Davidson, Brian P; Xie, Aris; Wu, Melinda D; Yadava, Mrinal; Qi, Yue; Liang, Sherry; Chon, Chae Ryung; Ammi, Azzdine Y; Field, Joshua; Harmann, Leanne; Chilian, William M; Linden, Joel; Lindner, Jonathan R
2017-03-28
Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for 10 minutes after intravenous injection of 2×10 8 lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signaling pathways were assessed by studying interventions that (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or K ATP channels; or (3) inhibited downstream signaling pathways involving endothelial nitric oxide synthase or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease. Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hours in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with sickle cell disease. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced an ≈40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or adenosine produced by ectonucleotidase activity. Combined indomethacin and inhibition of
Clinical workflow for spinal curvature measurement with portable ultrasound
NASA Astrophysics Data System (ADS)
Tabanfar, Reza; Yan, Christina; Kempston, Michael; Borschneck, Daniel; Ungi, Tamas; Fichtinger, Gabor
2016-03-01
PURPOSE: Spinal curvature monitoring is essential in making treatment decisions in scoliosis. Monitoring entails radiographic examinations, however repeated ionizing radiation exposure has been shown to increase cancer risk. Ultrasound does not emit ionizing radiation and is safer for spinal curvature monitoring. We investigated a clinical sonography protocol and challenges associated with position-tracked ultrasound in spinal curvature measurement in scoliosis. METHODS: Transverse processes were landmarked along each vertebra using tracked ultrasound snapshots. The transverse process angle was used to determine the orientation of each vertebra. We tested our methodology on five patients in a local pediatric scoliosis clinic, comparing ultrasound to radiographic curvature measurements. RESULTS: Despite strong correlation between radiographic and ultrasound curvature angles in phantom studies, we encountered new challenges in the clinical setting. Our main challenge was differentiating transverse processes from ribs and other structures during landmarking. We observed up to 13° angle variability for a single vertebra and a 9.85° +/- 10.81° difference between ultrasound and radiographic Cobb angles for thoracic curvatures. Additionally, we were unable to visualize anatomical landmarks in the lumbar region where soft tissue depth was 25-35mm. In volunteers with large Cobb angles (greater than 40° thoracic and 60° lumbar), we observed spinal protrusions resulting in incomplete probe-skin contact and partial ultrasound images not suitable for landmarking. CONCLUSION: Spinal curvature measurement using tracked ultrasound is viable on phantom spine models. In the clinic, new challenges were encountered which must be resolved before a universal sonography protocol can be developed.
Calibration and Evaluation of Ultrasound Thermography Using Infrared Imaging.
Hsiao, Yi-Sing; Deng, Cheri X
2016-02-01
Real-time monitoring of the spatiotemporal evolution of tissue temperature is important to ensure safe and effective treatment in thermal therapies including hyperthermia and thermal ablation. Ultrasound thermography has been proposed as a non-invasive technique for temperature measurement, and accurate calibration of the temperature-dependent ultrasound signal changes against temperature is required. Here we report a method that uses infrared thermography for calibration and validation of ultrasound thermography. Using phantoms and cardiac tissue specimens subjected to high-intensity focused ultrasound heating, we simultaneously acquired ultrasound and infrared imaging data from the same surface plane of a sample. The commonly used echo time shift-based method was chosen to compute ultrasound thermometry. We first correlated the ultrasound echo time shifts with infrared-measured temperatures for material-dependent calibration and found that the calibration coefficient was positive for fat-mimicking phantom (1.49 ± 0.27) but negative for tissue-mimicking phantom (-0.59 ± 0.08) and cardiac tissue (-0.69 ± 0.18°C-mm/ns). We then obtained the estimation error of the ultrasound thermometry by comparing against the infrared-measured temperature and revealed that the error increased with decreased size of the heated region. Consistent with previous findings, the echo time shifts were no longer linearly dependent on temperature beyond 45°C-50°C in cardiac tissues. Unlike previous studies in which thermocouples or water bath techniques were used to evaluate the performance of ultrasound thermography, our results indicate that high-resolution infrared thermography is a useful tool that can be applied to evaluate and understand the limitations of ultrasound thermography methods. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
CT and Ultrasound Guided Stereotactic High Intensity Focused Ultrasound (HIFU)
NASA Astrophysics Data System (ADS)
Wood, Bradford J.; Yanof, J.; Frenkel, V.; Viswanathan, A.; Dromi, S.; Oh, K.; Kruecker, J.; Bauer, C.; Seip, R.; Kam, A.; Li, K. C. P.
2006-05-01
To demonstrate the feasibility of CT and B-mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non-thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position-sensing arm and an active six degree-of-freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2-4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre-clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre-clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non-enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre-clinical models may be translated to large
Multicarrier airborne ultrasound transmission with piezoelectric transducers.
Ens, Alexander; Reindl, Leonhard M
2015-05-01
In decentralized localization systems, the received signal has to be assigned to the sender. Therefore, longrange airborne ultrasound communication enables the transmission of an identifier of the sender within the ultrasound signal to the receiver. Further, in areas with high electromagnetic noise or electromagnetic free areas, ultrasound communication is an alternative. Using code division multiple access (CDMA) to transmit data is ineffective in rooms due to high echo amplitudes. Further, piezoelectric transducers generate a narrow-band ultrasound signal, which limits the data rate. This work shows the use of multiple carrier frequencies in orthogonal frequency division multiplex (OFDM) and differential quadrature phase shift keying modulation with narrowband piezoelectric devices to achieve a packet length of 2.1 ms. Moreover, the adapted channel coding increases data rate by correcting transmission errors. As a result, a 2-carrier ultrasound transmission system on an embedded system achieves a data rate of approximately 5.7 kBaud. Within the presented work, a transmission range up to 18 m with a packet error rate (PER) of 13% at 10-V supply voltage is reported. In addition, the transmission works up to 22 m with a PER of 85%. Moreover, this paper shows the accuracy of the frame synchronization over the distance. Consequently, the system achieves a standard deviation of 14 μs for ranges up to 10 m.
Portable bladder ultrasound: an evidence-based analysis.
2006-01-01
The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary
Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.
Stride, E P; Coussios, C C
2010-01-01
Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.
The role for peer-assisted ultrasound teaching in medical school.
Dickerson, Jonathan; Paul, Katie; Vila, Pierre; Whiticar, Rebecca
2017-06-01
Bedside ultrasonography has an increasing role in medicine yet medical students have limited exposure. Although countless hours are devoted to plain radiograph and electrocardiogram (ECG) interpretation, ultrasound is frequently glossed over. Yet this imaging modality could enhance students' understanding of anatomy, physiology and pathology, and may increase their integration into hospital teams. We aimed to investigate whether a peer-assisted ultrasound course has a place within the undergraduate medical curriculum. We describe the implementation of a course and discuss its acceptability and utility in student education. Bedside ultrasonography has an increasing role in medicine yet medical students have limited exposure METHODS: Following consultation with the medical school, an improved ultrasonography course was developed with expert guidance from an ultrasonographer and with new equipment. Sessions involved peer-tutors teaching ultrasonography techniques to medical students during emergency medicine placements. Tutees completed questionnaires to assess the quality and perceived benefits of the course and of learning ultrasonography. Both quantitative and thematic analyses of the responses were conducted by the authors. Over a period of 8 months, 105 medical students received teaching across four sessions. A total of 103 students (98%) returned questionnaires on their evaluation of the course and tutors, and on their confidence in using ultrasound. Ninety-eight per cent felt that the teaching was well delivered, 100 per cent felt that their knowledge of ultrasound had improved and 100 per cent would recommend the course. The peer-assisted ultrasound course described here enabled the majority of students to feel confident gaining elementary ultrasound views, and performing abdominal aneurysm screening and trauma assessments: techniques that they could hopefully put to use during their placements. The peer-assisted model has an acceptable role in teaching
Lu, Ko-Hsiu; Chen, Pei-Ni; Hsieh, Yi-Hsien; Lin, Chin-Yin; Cheng, Fu-Yuan; Chiu, Peng-Chou; Chu, Shu-Chen; Hsieh, Yih-Shou
2016-11-01
Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 μM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin. 3-hydroxyflavone significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-steroid receptor coactivator (Src), p-mitogen/extracellular signal-regulated kinase (MEK)1/2, p-myosin light chain (MLC)2 Ser19, epithelial cell adhesion molecule, Ras homolog gene family (Rho)A and fibronectin expressions. 3-hydroxyflavone also affected the epithelial-mesenchymal transition (EMT) by down-regulating expressions of Vimentin and α-catenin with activation of the transcription factor Slug. In nude mice xenograft model and tail vein injection model showed that 3-hydroxyflavone reduced 143B tumor growth and lung metastasis. 3-hydroxyflavone possesses the anti-metastatic activity of U2OS and 143B cells by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and suppresses 143B tumor growth in vivo. This may lead to clinical trials of osteosarcoma chemotherapy to confirm the promising result in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.
Zhou, Wei; Wang, Jingjing; Wang, Kaiyue; Huang, Bin; Niu, Lili; Li, Fei; Cai, Feiyan; Chen, Yan; Liu, Xin; Zhang, Xiaoyan; Cheng, Hankui; Kang, Lijun; Meng, Long; Zheng, Hairong
2017-05-16
Ultrasound neuro-modulation has gained increasing attention as a non-invasive method. In this paper, we present an ultrasound neuro-modulation chip, capable of initiating reversal behaviour and activating neurons of C. elegans under the stimulation of a single-shot, short-pulsed ultrasound. About 85.29% ± 6.17% of worms respond to the ultrasound stimulation exhibiting reversal behaviour. Furthermore, the worms can adapt to the ultrasound stimulation with a lower acoustic pulse duration of stimulation. In vivo calcium imaging shows that the activity of ASH, a polymodal sensory neuron in C. elegans, can be directly evoked by the ultrasound stimulation. On the other hand, AFD, a thermal sensitive neuron, cannot be activated by the ultrasound stimulation using the same parameter and the temperature elevation during the stimulation process is relatively small. Consistent with the calcium imaging results, the tax-4 mutants, which are insensitive to temperature increase, do not show a significant difference in avoidance probability compared to the wild type. Therefore, the mechanical effects induced by ultrasound are the main reason for neural and behavioural modulation of C. elegans. With the advantages of confined acoustic energy on the surface, compatible with standard calcium imaging, this neuro-modulation chip could be a powerful tool for revealing the molecular mechanisms of ultrasound neuro-modulation.
Ma, Irene W Y; Arishenkoff, Shane; Wiseman, Jeffrey; Desy, Janeve; Ailon, Jonathan; Martin, Leslie; Otremba, Mirek; Halman, Samantha; Willemot, Patrick; Blouw, Marcus
2017-09-01
Bedside point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. At present, no consensus exists for what POCUS curriculum is appropriate for internal medicine residency training programs. This document details the consensus-based recommendations by the Canadian Internal Medicine Ultrasound (CIMUS) group, comprising 39 members, representing 14 institutions across Canada. Guiding principles for selecting curricular content were determined a priori. Consensus was defined as agreement by at least 80% of the members on POCUS applications deemed appropriate for teaching and assessment of trainees in the core (internal medicine postgraduate years [PGY] 1-3) and expanded (general internal medicine PGY 4-5) training programs. We recommend four POCUS applications for the core PGY 1-3 curriculum (inferior vena cava, lung B lines, pleural effusion, and abdominal free fluid) and three ultrasound-guided procedures (central venous catheterization, thoracentesis, and paracentesis). For the expanded PGY 4-5 curriculum, we recommend an additional seven applications (internal jugular vein, lung consolidation, pneumothorax, knee effusion, gross left ventricular systolic function, pericardial effusion, and right ventricular strain) and four ultrasound-guided procedures (knee arthrocentesis, arterial line insertion, arterial blood gas sampling, and peripheral venous catheterization). These recommendations will provide a framework for training programs at a national level.
A motorized ultrasound system for MRI-ultrasound fusion guided prostatectomy
NASA Astrophysics Data System (ADS)
Seifabadi, Reza; Xu, Sheng; Pinto, Peter; Wood, Bradford J.
2016-03-01
Purpose: This study presents MoTRUS, a motorized transrectal ultrasound system, to enable remote navigation of a transrectal ultrasound (TRUS) probe during da Vinci assisted prostatectomy. MoTRUS not only provides a stable platform to the ultrasound probe, but also allows the physician to navigate it remotely while sitting on the da Vinci console. This study also presents phantom feasibility study with the goal being intraoperative MRI-US image fusion capability to bring preoperative MR images to the operating room for the best visualization of the gland, boundaries, nerves, etc. Method: A two degree-of-freedom probe holder is developed to insert and rotate a bi-plane transrectal ultrasound transducer. A custom joystick is made to enable remote navigation of MoTRUS. Safety features have been considered to avoid inadvertent risks (if any) to the patient. Custom design software has been developed to fuse pre-operative MR images to intraoperative ultrasound images acquired by MoTRUS. Results: Remote TRUS probe navigation was evaluated on a patient after taking required consents during prostatectomy using MoTRUS. It took 10 min to setup the system in OR. MoTRUS provided similar capability in addition to remote navigation and stable imaging. No complications were observed. Image fusion was evaluated on a commercial prostate phantom. Electromagnetic tracking was used for the fusion. Conclusions: Motorized navigation of the TRUS probe during prostatectomy is safe and feasible. Remote navigation provides physician with a more precise and easier control of the ultrasound image while removing the burden of manual manipulation of the probe. Image fusion improved visualization of the prostate and boundaries in a phantom study.
Schlaepfer, D D; Hanks, S K; Hunter, T; van der Geer, P
The cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine-phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro. Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway.
Santos, Philipe; Aguiar, Ana C; Barbero, Gerardo F; Rezende, Camila A; Martínez, Julian
2015-01-01
Extracts from malagueta pepper (Capsicum frutescens L.) were obtained using supercritical fluid extraction (SFE) assisted by ultrasound, with carbon dioxide as solvent at 15MPa and 40°C. The SFE global yield increased up to 77% when ultrasound waves were applied, and the best condition of ultrasound-assisted extraction was ultrasound power of 360W applied during 60min. Four capsaicinoids were identified in the extracts and quantified by high performance liquid chromatography. The use of ultrasonic waves did not influence significantly the capsaicinoid profiles and the phenolic content of the extracts. However, ultrasound has enhanced the SFE rate. A model based on the broken and intact cell concept was adequate to represent the extraction kinetics and estimate the mass transfer coefficients, which were increased with ultrasound. Images obtained by field emission scanning electron microscopy showed that the action of ultrasonic waves did not cause cracks on the cell wall surface. On the other hand, ultrasound promoted disturbances in the vegetable matrix, leading to the release of extractable material on the solid surface. The effects of ultrasound were more significant on SFE from larger solid particles. Copyright © 2014 Elsevier B.V. All rights reserved.
Focused ultrasound in ophthalmology
Silverman, Ronald H
2016-01-01
The use of focused ultrasound to obtain diagnostically significant information about the eye goes back to the 1950s. This review describes the historical and technological development of ophthalmic ultrasound and its clinical application and impact. Ultrasound, like light, can be focused, which is crucial for formation of high-resolution, diagnostically useful images. Focused, single-element, mechanically scanned transducers are most common in ophthalmology. Specially designed transducers have been used to generate focused, high-intensity ultrasound that through thermal effects has been used to treat glaucoma (via ciliodestruction), tumors, and other pathologies. Linear and annular transducer arrays offer synthetic focusing in which precise timing of the excitation of independently addressable array elements allows formation of a converging wavefront to create a focus at one or more programmable depths. Most recently, linear array-based plane-wave ultrasound, in which the array emits an unfocused wavefront and focusing is performed solely on received data, has been demonstrated for imaging ocular anatomy and blood flow. While the history of ophthalmic ultrasound extends back over half-a-century, new and powerful technologic advances continue to be made, offering the prospect of novel diagnostic capabilities. PMID:27757007
Focused ultrasound in ophthalmology.
Silverman, Ronald H
2016-01-01
The use of focused ultrasound to obtain diagnostically significant information about the eye goes back to the 1950s. This review describes the historical and technological development of ophthalmic ultrasound and its clinical application and impact. Ultrasound, like light, can be focused, which is crucial for formation of high-resolution, diagnostically useful images. Focused, single-element, mechanically scanned transducers are most common in ophthalmology. Specially designed transducers have been used to generate focused, high-intensity ultrasound that through thermal effects has been used to treat glaucoma (via ciliodestruction), tumors, and other pathologies. Linear and annular transducer arrays offer synthetic focusing in which precise timing of the excitation of independently addressable array elements allows formation of a converging wavefront to create a focus at one or more programmable depths. Most recently, linear array-based plane-wave ultrasound, in which the array emits an unfocused wavefront and focusing is performed solely on received data, has been demonstrated for imaging ocular anatomy and blood flow. While the history of ophthalmic ultrasound extends back over half-a-century, new and powerful technologic advances continue to be made, offering the prospect of novel diagnostic capabilities.
Mechanotransduction of Ultrasound is Frequency Dependent Below the Cavitation Threshold
Louw, Tobias M.; Budhiraja, Gaurav; Viljoen, Hendrik J.; Subramanian, Anuradha
2013-01-01
This study provides evidence that low-intensity ultrasound directly affects nuclear processes, and the magnitude of the effect varies with frequency. In particular, we show that the transcriptional induction of first load-inducible genes, which is independent of new protein synthesis, is frequency dependent. Bovine chondrocytes were exposed to low-intensity below the cavitational threshold) ultrasound at 2,5 and 8 MHz. Ultrasound elevated the expression of early response genes c-Fos, c-Jun and c-Myc, maximized at 5 MHz. The phosphorylated ERK inhibitor PD98059 abrogated any increase in c-series gene expression, suggesting that signaling occurs via the MAPPK/ERK pathway. However, phosphorylated ERK levels did not change with ultrasound frequency, indicating that processes downstream of ERK phosphorylation (such as nuclear transport and chromatin reorganization) respond to ultrasound with frequency dependence. A quantitative, biphasic mathematical model based on Biot theory predicted that cytoplasmic and nuclear stress is maximized at 5.2 ± 0.8 MHz for a chondrocyte, confirming experimental measurements. PMID:23562015
Application of airborne ultrasound in the convective drying of fruits and vegetables: A review.
Fan, Kai; Zhang, Min; Mujumdar, Arun S
2017-11-01
The application of airborne ultrasound is a promising technology in the drying of foods, particularly to fruits and vegetables. In this paper, designs of dryers using ultrasound to combine the convective drying process are described. The main factors affecting the drying kinetics with the ultrasound application are discussed. The results show that the ultrasound application accelerated the drying kinetics. Ultrasound application during the convective drying of fruits and vegetables shorten the drying time. Ultrasound application can produce an increase of the effective moisture diffusivity and the mass transfer coefficient. The influence of ultrasound on physical and chemical parameters evaluating the product quality is reviewed. Ultrasound application can decrease the total color change, reveal a low water activity and reduce the loss of some nutrient elements. Meanwhile, ultrasound application can also better preserve the microstructure of fruits and vegetables in comparison to convective drying. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Gordon, S. E.; Fluck, M.; Booth, F. W.
2001-01-01
This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by < or =1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.
Li, Suyun; Yang, Xue; Zhang, Yanyan; Ma, Haile; Liang, Qiufang; Qu, Wenjuan; He, Ronghai; Zhou, Cunshan; Mahunu, Gustav Komla
2016-07-01
The objectives of this study were to investigate the effects of multi-frequency energy-gathered ultrasound (MFEGU) and MFEGU assisted alkaline pretreatments on the enzymolysis and the mechanism of two pretreatments accelerating the rice protein (RP) proteolysis process. The results showed that MFEGU and MFEGU assisted alkaline pretreatments improved significantly (P<0.05) the degree of hydrolysis (DH) and the protein elution amount of RP. Furthermore under the same DH conditions, ultrasound and ultrasound assisted alkaline pretreatments were more save the enzymolysis time than the unpretreatment. The changes in UV-vis spectra, fluorescence emission spectra indicated unfolding and destruction of RP by MFEGU and MFEGU assisted alkaline pretreatments. The circular dichroism analysis showed that both pretreatments decreased α-helix but increased β-sheet and random coil of RP. Amino acid composition revealed that MFEGU and MFEGU assisted alkaline pretreatments could increase the protein elution amount and the ratio of hydrophobic amino acids. Atomic force microscopy (AFM) indicated that both pretreatments destroyed the microstructures and reduced the particle size of RP. Therefore, MFEGU and MFEGU assisted alkaline pretreatments are beneficial to improving the degree of hydrolysis due to its sonochemistry effect on the molecular conformation as well as on the microstructure of protein. Copyright © 2015 Elsevier B.V. All rights reserved.
Simulation Study of Effects of the Blind Deconvolution on Ultrasound Image
NASA Astrophysics Data System (ADS)
He, Xingwu; You, Junchen
2018-03-01
Ultrasonic image restoration is an essential subject in Medical Ultrasound Imaging. However, without enough and precise system knowledge, some traditional image restoration methods based on the system prior knowledge often fail to improve the image quality. In this paper, we use the simulated ultrasound image to find the effectiveness of the blind deconvolution method for ultrasound image restoration. Experimental results demonstrate that the blind deconvolution method can be applied to the ultrasound image restoration and achieve the satisfactory restoration results without the precise prior knowledge, compared with the traditional image restoration method. And with the inaccurate small initial PSF, the results shows blind deconvolution could improve the overall image quality of ultrasound images, like much better SNR and image resolution, and also show the time consumption of these methods. it has no significant increasing on GPU platform.
Unpowered wireless generation and sensing of ultrasound
NASA Astrophysics Data System (ADS)
Huang, Haiying
2013-04-01
This paper presents a wireless ultrasound pitch-catch system that demonstrates the wireless generation and sensing of ultrasounds based on the principle of frequency conversion. The wireless ultrasound pitch-catch system consists of a wireless interrogator and two wireless ultrasound transducers. The wireless interrogator generates an ultrasound-modulated signal and a carrier signal, both at the microwave frequency, and transmits these two signals to the wireless ultrasound actuator using a pair of antennas. Upon receiving these two signals, the wireless ultrasound actuator recovers the ultrasound excitation signal using a passive mixer and then supplies it to a piezoelectric wafer sensor for ultrasound generation in the structure. For wireless ultrasound sensing, the frequency conversion process is reversed. The ultrasound sensing signal is up-converted to a microwave signal by the wireless ultrasound sensor and is recovered at the wireless interrogator using a homodyne receiver. To differentiate the wireless actuator from the wireless sensor, each wireless transducer is equipped with a narrowband microwave filter so that it only responds to the carrier frequency that matches the filter's operation bandwidth. The principle of operation of the wireless pitch-catch system, the hardware implementation, and the associated data processing algorithm to recover the ultrasound signal from the wirelessly received signal are described. The wirelessly acquired ultrasound signal is compared with those acquired using wired connection in both time and frequency domain.
3-D ultrasound guidance of surgical robotics: a feasibility study.
Pua, Eric C; Fronheiser, Matthew P; Noble, Joanna R; Light, Edward D; Wolf, Patrick D; von Allmen, Daniel; Smith, Stephen W
2006-11-01
Laparoscopic ultrasound has seen increased use as a surgical aide in general, gynecological, and urological procedures. The application of real-time, three-dimensional (RT3D) ultrasound to these laparoscopic procedures may increase information available to the surgeon and serve as an additional intraoperative guidance tool. The integration of RT3D with recent advances in robotic surgery also can increase automation and ease of use. In this study, a 1-cm diameter probe for RT3D has been used laparoscopically for in vivo imaging of a canine. The probe, which operates at 5 MHz, was used to image the spleen, liver, and gall bladder as well as to guide surgical instruments. Furthermore, the three-dimensional (3-D) measurement system of the volumetric scanner used with this probe was tested as a guidance mechanism for a robotic linear motion system in order to simulate the feasibility of RT3D/robotic surgery integration. Using images acquired with the 3-D laparoscopic ultrasound device, coordinates were acquired by the scanner and used to direct a robotically controlled needle toward desired in vitro targets as well as targets in a post-mortem canine. The rms error for these measurements was 1.34 mm using optical alignment and 0.76 mm using ultrasound alignment.
Palte, Howard D; Gayer, Steven; Arrieta, Esdras; Scot Shaw, Eric; Nose, Izuru; Lee, Elizabete; Arheart, Kristopher L; Dubovy, Sander; Birnbach, David J; Parel, Jean-Marie
2012-07-01
Since Atkinson's original description of retrobulbar block in 1936, needle-based anesthetic techniques have become integral to ophthalmic anesthesia. These techniques are unfortunately associated with rare, grave complications such as globe perforation. Ultrasound has gained widespread acceptance for peripheral nerve blockade, but its translation to ocular anesthesia has been hampered because sonic energy, in the guise of thermal or biomechanical insult, is potentially injurious to vulnerable eye tissue. The US Food and Drug Administration (FDA) has defined guidelines for safe use of ultrasound for ophthalmic examination, but most ultrasound devices used by anesthesiologists are not FDA-approved for ocular application because they generate excessive energy. Regulating agencies state that ultrasound examinations can be safely undertaken as long as tissue temperatures do not increase >1.5°C above physiological levels. Using a rabbit model, we investigated the thermal and mechanical ocular effects after prolonged ultrasonic exposure to single orbital- and nonorbital-rated devices. In a dual-phase study, aimed at detecting ocular injury, the eyes of 8 rabbits were exposed to continuous 10-minute ultrasound examinations from 2 devices: (1) the Sonosite Micromaxx (nonorbital rated) and (2) the Sonomed VuMax (orbital rated) machines. In phase I, temperatures were continuously monitored via thermocouples implanted within specific eye structures (n = 4). In phase II the eyes were subjected to ultrasonic exposure without surgical intervention (n = 4). All eyes underwent light microscopy examinations, followed at different intervals by histology evaluations conducted by an ophthalmic pathologist. Temperature changes were monitored in the eyes of 4 rabbits. The nonorbital-rated transducer produced increases in ocular tissue temperature that surpassed the safe limit (increases >1.5°C) in the lens of 3 rabbits (at 5.0, 5.5, and 1.5 minutes) and cornea of 2 rabbits (both at 1
Palte, Howard D.; Gayer, Steven; Arrieta, Esdras; Shaw, Eric Scot; Nose, Izuru; Lee, Elizabete; Arheart, Kristopher L.; Dubovy, Sander; Birnbach, David J.; Parel, Jean-Marie
2012-01-01
Background Since Atkinson’s original description of retrobulbar block in 1936, needle-based anesthetic techniques have become integral to ophthalmic anesthesia. These techniques are unfortunately associated with rare, grave complications such as globe perforation. Ultrasound has gained widespread acceptance for peripheral nerve blockade but its translation to ocular anesthesia has been hampered because sonic energy, in the guise of thermal or biomechanical insult, is potentially injurious to vulnerable eye tissue. The United States Food and Drug Administration have defined guidelines for safe use of ultrasound for ophthalmic examination but most ultrasound devices used by anesthesiologists are not Food and Drug Administration-approved for ocular application because they generate excessive energy. Regulating agencies state that ultrasound examination can be safely undertaken as long as tissue temperatures do not increase >1.5°C above physiological levels. Methods Using a rabbit model, we investigated the thermal and mechanical ocular effects after prolonged ultrasonic exposure to single orbital and non-orbital-rated devices. In a dual-phase study, aimed at detecting ocular injury, the eyes of 8 rabbits were exposed to continuous 10-minute ultrasound examinations from two devices: 1) the Sonosite Micromaxx (non-orbital-rated) and 2) the Sonomed VuMax (orbital-rated) machines. In Phase I temperatures were continuously monitored via thermocouples implanted within specific eye structures (n=4). In Phase II the eyes were subjected to ultrasonic exposure without surgical intervention (n=4). All eyes underwent light microscopy examinations followed, at different intervals, by histology evaluations conducted by an ophthalmic pathologist. Results Temperature changes were monitored in the eyes of four rabbits. The non-orbital-rated transducer produced increases in ocular tissue temperature that surpassed the safe limit (increases> 1.50C ) in the lens of three rabbits (at 5
Introduction of basic obstetrical ultrasound screening in undergraduate medical education.
Hamza, A; Solomayer, E-F; Takacs, Z; Juhasz-Boes, I; Joukhadar, R; Radosa, J C; Mavrova, R; Marc, W; Volk, T; Meyberg-Solomayer, G
2016-09-01
Teaching ultrasound procedures to undergraduates has recently been proposed to improve the quality of medical education. We address the impact of applying standardized ultrasound teaching to our undergraduates. Medical students received an additional theoretical and practical course involving hands-on ultrasound screening during their mandatory practical training week in obstetrics and gynecology. The students' theoretical knowledge and fetal image recognition skills were tested before and after the course. After the course, the students were asked to answer a course evaluation questionnaire. To standardize the teaching procedure, we used Peyton's 4-Step Approach to teach the skills needed for a German Society of Ultrasound in Medicine Level 1 ultrasound examiner. The multiple-choice question scores after the course showed statistically significant improvement (50 vs. 80 %; P < 0.001). The questionnaire revealed that students were satisfied with the course, felt that it increased their ultrasound knowledge, and indicated that they wanted more sonographic hands-on training in both obstetrics and gynecology and other medical fields. Using practical, hands-on medical teaching is an emerging method for undergraduate education that should be further evaluated, standardized, and developed.
Determining Directions of Ultrasound in Solids
NASA Technical Reports Server (NTRS)
Generazio, Edward R.; Roth, Don J.
1987-01-01
Ultrasound shadows cast by grooves. Improved method for determining direction of ultrasound in materials is shadow method using Scanning laser acoustic microscopy (SLAM). Direction of ultrasound calculated from dimensions of groove and portion of surface groove shields from ultrasound. Method has variety of applications in nontraditional quality-control applications.
Jiang, Jun-Hong; Turner, J Francis; Huang, Jian-An
2015-12-01
TBNA through the flexible bronchoscope is a 37-year-old technology that utilizes a TBNA needle to puncture the bronchial wall and obtain specimens of peribronchial and mediastinal lesions through the flexible bronchoscope for the diagnosis of benign and malignant diseases in the mediastinum and lung. Since 2002, the Olympus Company developed the first generation ultrasound equipment for use in the airway, initially utilizing an ultrasound probe introduced through the working channel followed by incoroporation of a fixed linear ultrasound array at the distal tip of the bronchoscope. This new bronchoscope equipped with a convex type ultrasound probe on the tip was subsequently introduced into clinical practice. The convex probe (CP)-EBUS allows real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal and hilar lymph nodes. EBUS-TBNA is a minimally invasive procedure performed under local anesthesia that has been shown to have a high sensitivity and diagnostic yield for lymph node staging of lung cancer. In 10 years of EBUS development, the Olympus Company developed the second generation EBUS bronchoscope (BF-UC260FW) with the ultrasound image processor (EU-M1), and in 2013 introduced a new ultrasound image processor (EU-M2) into clinical practice. FUJI company has also developed a curvilinear array endobronchial ultrasound bronchoscope (EB-530 US) that makes it easier for the operator to master the operation of the ultrasonic bronchoscope. Also, the new thin convex probe endobronchial ultrasound bronchoscope (TCP-EBUS) is able to visualize one to three bifurcations distal to the current CP-EBUS. The emergence of EBUS-TBNA has also been accompanied by innovation in EBUS instruments. EBUS elastography is, then, a new technique for describing the compliance of structures during EBUS, which may be of use in the determination of metastasis to the mediastinal and hilar lymph nodes. This article describes these new EBUS
Investigation of Post-mortem Tissue Effects Using Long-time Decorrelation Ultrasound
NASA Astrophysics Data System (ADS)
Csány, Gergely; Balogh, Lajos; Gyöngy, Miklós
Decorrelation ultrasound is being increasingly used to investigate long-term biological phenomena. In the current work, ultrasound image sequences of mice who did not survive anesthesia (in a separate investigation) were analyzed and post-mortem tissue effects were observed via decorrelation calculation. A method was developed to obtain a quantitative parameter characterizing the rate of decorrelation. The results show that ultrasound decorrelation imaging is an effective method of observing post-mortem tissue effects and point to further studies elucidating the mechanism behind these effects.
Abdominal ultrasound and medical education.
García de Casasola Sánchez, G; Torres Macho, J; Casas Rojo, J M; Cubo Romano, P; Antón Santos, J M; Villena Garrido, V; Diez Lobato, R
2014-04-01
Ultrasound is a very versatile diagnostic modality that permits real-time visualization of multiple internal organs. It is of invaluable help for the physical examination of the patients. To assess if ultrasound can be incorporated into medical education and if the students can perform a basic abdominal ultrasound examination without the necessity of a long period of training. Twelve medical students were trained in basic abdominal ultrasound during a 15-h training program including a 5-h theoretical and practical course and supervised practice in 20 selected patients. Subsequently, we conducted an evaluation test that assessed the ability of students to obtain the ultrasound views and to detect various pathologies in five different patients. The students were able to correctly identify the abdominal views more than 90% of the times. This percentage was only lower (80%) in the right subcostal view to locate the gallbladder. The accuracy or global efficiency of the ultrasound for the diagnosis of relevant pathological findings of the patients was greater than 90% (91.1% gallstones, abdominal aortic aneurysm 100%; splenomegaly 98.3%, ascites 100%; dilated inferior vena cava 100%; acute urinary retention 100%). The ultrasound may be a feasible learning tool in medical education. Ultrasound can help students to improve the physical examination. Copyright © 2013 Elsevier España, S.L. All rights reserved.
[Basics of emergency ultrasound].
Schellhaas, S; Breitkreutz, R
2012-09-05
Focused ultrasound is a key methodology of critical care medicine. By referencing few ultrasound differential diagnosis, it is possible to identifying in real-time the reason of the critical state of a patient. Therefore typical focused ultrasound protocols were developed. The well known Focused Assessment with Sonography for trauma (FAST) was incorporated into the Advanced Trauma Life Support (ATLS) for shock room. Focused echocardiographic evaluation in life support (FEEL) has been designed to be conformed with the universal Advanced Life Support (ALS) algorithm and to identify treatable conditions such as acute right ventricular pressure overload in pulmonary embolism, hypovolemia, or pericardial effusion/tamponade. Using lung ultrasound one can differentiate pulmonary edema, pleural effusion or pneumothorax.
Ultrasound generation with high power and coil only EMAT concepts.
Rueter, Dirk; Morgenstern, Tino
2014-12-01
Electro-magnetic acoustic transducers (EMATs) are intended as non-contact and non-destructive ultrasound transducers for metallic material. The transmitted intensities from EMATS are modest, particularly at notable lift off distances. Some time ago a concept for a "coil only EMAT" was presented, without static magnetic field. In this contribution, such compact "coil only EMATs" with effective areas of 1-5cm(2) were driven to excessive power levels at MHz frequencies, using pulsed power technologies. RF induction currents of 10kA and tens of Megawatts are applied. With increasing power the electroacoustic conversion efficiency also increases. The total effect is of second order or quadratic, therefore non-linear and progressive, and yields strong ultrasound signals up to kW/cm(2) at MHz frequencies in the metal. Even at considerable lift off distances (cm) the ultrasound can be readily detected. Test materials are aluminum, ferromagnetic steel and stainless steel (non-ferromagnetic). Thereby, most metal types are represented. The technique is compared experimentally with other non-contact methods: laser pulse induced ultrasound and spark induced ultrasound, both damaging to the test object's surface. At small lift off distances, the intensity from this EMAT concept clearly outperforms the laser pulses or heavy spark impacts. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Cachard, Christian; Basset, Olivier
While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.
Echography - eye orbit; Ultrasound - eye orbit; Ocular ultrasonography; Orbital ultrasonography ... eye is numbed with medicine (anesthetic drops). The ultrasound wand (transducer) is placed against the front surface ...
NASA Astrophysics Data System (ADS)
Hadjisavvas, V.; Damianou, C.
2011-09-01
In this paper a simulation model for predicting the temperature during the application of MR-guided focused ultrasound for stroke treatment using pulsed ultrasound is presented. A single element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at either 0.5 MHz or 1 MHz was considered. The power field was estimated using the KZK model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (power, pulse duration, duty factor and pulse repetition frequency) that maintain a temperature increase of less than 1 °C during the application of a pulse ultrasound protocol. It was found that the temperature change increases linearly with duty factor. The higher the power, the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. The higher the frequency the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. Finally, the deeper the target, the higher the duty factor needed to keep the temperature change to the safe limit of 1 °C. The simulation model was tested in brain tissue during the application of pulse ultrasound and the measured temperature was in close agreement with the simulated temperature. This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, duty factor, pulse repetition frequency) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model could be tested soon during stroke clinical trials.
Zhang, Siyuan; Zong, Yujin; Wan, Mingxi; Yu, Xiaojun; Fu, Quanyou; Ding, Ting; Zhou, Fanyu; Wang, Supin
2012-06-01
This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.
Breast ultrasound tomography with two parallel transducer arrays
NASA Astrophysics Data System (ADS)
Huang, Lianjie; Shin, Junseob; Chen, Ting; Lin, Youzuo; Gao, Kai; Intrator, Miranda; Hanson, Kenneth
2016-03-01
Breast ultrasound tomography is an emerging imaging modality to reconstruct the sound speed, density, and ultrasound attenuation of the breast in addition to ultrasound reflection/beamforming images for breast cancer detection and characterization. We recently designed and manufactured a new synthetic-aperture breast ultrasound tomography prototype with two parallel transducer arrays consisting of a total of 768 transducer elements. The transducer arrays are translated vertically to scan the breast in a warm water tank from the chest wall/axillary region to the nipple region to acquire ultrasound transmission and reflection data for whole-breast ultrasound tomography imaging. The distance of these two ultrasound transducer arrays is adjustable for scanning breasts with different sizes. We use our breast ultrasound tomography prototype to acquire phantom and in vivo patient ultrasound data to study its feasibility for breast imaging. We apply our recently developed ultrasound imaging and tomography algorithms to ultrasound data acquired using our breast ultrasound tomography system. Our in vivo patient imaging results demonstrate that our breast ultrasound tomography can detect breast lesions shown on clinical ultrasound and mammographic images.
Fakoya, Francis A; du Plessis, Maira; Gbenimacho, Ikechi B
2016-01-01
Objectives In recent years, the use and portability of ultrasound has threatened the utility of the stethoscope, with many debating and even advocating its replacement. The authors set out to assess opinions in this regard among faculty within a medical school and specifically within an anatomy department where ultrasound is incorporated into the curriculum from the first term. Methods A debate was elicited during a biweekly Anatomy Journal Club session and was centered on three published papers presented. Several questions were raised regarding the possible replacement of stethoscope – the value of early exposure to students as well as how ultrasound and stethoscope should be considered by physicians, students, and teachers. Results The general consensus was that the stethoscope should not be replaced but should be used in conjunction with emerging portable ultrasound. Caution was given that technology could “overcomplicate” diagnosis and lead to increased tests resulting in increased cost of care. In terms of exposing students to ultrasound, just as the stethoscope requires practice to use effectively, so does the ultrasound and should be introduced as early on as possible. As is the case with the stethoscope, students may not initially appreciate all the finer details on ultrasound; however, continual use would improve skill. Conclusion The stethoscope should always remain part of the physical examination and ultrasound should be used in addition to, not replacement of. As technology advances the need for apprenticeship, training increases and students of the medical profession should be exposed to these technologies as early as possible. Hence, it is not yet time to archive the stethoscope. Perhaps never. PMID:27471420
Ultrasound Accuracy in Diagnosing Appendicitis in Obese Pediatric Patients.
Love, Bryan E; Camelo, Monica; Nouri, Sarvenaz; Kriger, Diego; Ludi, Daniel; Nguyen, Henry
2017-10-01
The use of ultrasound to diagnose appendicitis in pediatric patients has been growing with the improvement of ultrasound technology and operator skills, but its utility in the increasingly obese pediatric population has not been thoroughly investigated. A retrospective review of all pediatric (≤18 years old) patients with appendicitis who were admitted at a single hospital from 2014 to 2016 was conducted. Patients were stratified into body mass index (BMI) percentile categories based on the centers for disease control guidelines. Comparisons were then made. There were 231 patients with an average BMI percentile of 72.6; 99 (42.9%) who had an ultrasound, of which 54 (54.5%) were positive for acute appendicitis, whereas 43 (43.4%) were nondiagnostic. In patients who had a nondiagnostic ultrasound, 37 had a CT demonstrating acute appendicitis. These were compared with 123 patients who had CT alone demonstrating acute appendicitis. The CT-only group was older (12 vs 9, P < 0.005), tended to be male (78 (63%) vs 15 (41%), P = 0.019), had fewer operations performed (81 (66%) vs 30 (81%), P = 0.048) but had no significant difference in BMI percentile (75.8 vs 71.7, P = 0.465). Ultrasound had a 100 per cent positive predictive value in obese and overweight children. Ultrasound is a reliable study in obese and overweight pediatric patients with acute appendicitis.
Cell damage of hepatoma-22 cells exposed to continuous wave ultrasound.
Wang, Pan; Wang, Xiaobing; Liu, Quanhong
2012-01-01
The cellular response of hepatoma-22 cells to ultrasonic irradiation and the potential cause for the action were evaluated. Hepatoma-22 cells were subjected to ultrasound irradiation at a frequency of 2.17 MHz and a spatial average intensity of 1.6 W/cm2 for variable periods of time, and several biological parameters were analyzed. The terephthalic acid (TA) dosimetry method was used to evaluate the efficacies of irradiation parameters on the acoustic cavitation activity by monitoring hydroxyl radical (OH) production. Lactate dehydrogenase (LDH) leakage was assayed to investigate cell membrane integrity. The polarization value of fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured to monitor plasma membrane fluidity. The malonaldehyde content in cells was determined to reflect lipid peroxidation. Trypan blue exclusion was used to detect cell viability. Additionally, electron microscopy was used to observe morphological changes. The generation of intracellular reactive oxygen species, mitochondria swelling and the loss of mitochondria membrane potential were also investigated. The results showed that 1) the concentration of ·OH production by ultrasonic irradiation in air-saturated cell suspensions increased as ultrasound exposure time increased; 2) compared with control, lactate dehydrogenase leakage, the polarization value of 1,6-diphenyl-1,3,5-hexatriene, malonaldehyde content and cell lysis were significantly elevated when cells were treated by ultrasound for 60 s; 3) cytotoxicity by ultrasound irradiation was also accompanied by an increase in production of intracellular reactive oxygen species and dissipation of mitochondria membrane potential as well as by mitochondria swelling. Presently available information indicates that the plasma membrane and mitochondria are the main targets for ultrasound treatment, and free radicals formation such as ·OH due to ultrasound cavitation may play an important role in mediating these cellular response
Prostate ultrasound: back in business!
Crisan, Nicolae; Andras, Iulia; Radu, Corina; Andras, David; Coman, Radu-Tudor; Tucan, Paul; Pisla, Doina; Crisan, Dana; Coman, Ioan
2017-11-29
The use of grey scale prostate ultrasound decreased after the implementation of magnetic resonance imaging (MRI) for the diagnosis and evaluation of prostate cancer. The new developments, such as multiparametric ultrasound and MRI-ultrasound fusion technology, renewed the interest for this imaging method in the assessment of prostate cancer. The purpose of this paper was to review the current role of prostate ultrasound in the setting of these new applications. A thorough reevaluation of the selection criteria of the patients is required to assess which patients would benefit from multiparametric ultrasound, who wouldbenefit from multiparametric MRI or the combination of both to assist prostate biopsy in order to ensure the balance between overdiagnosis and underdiagnosis of prostate cancer.
NASA Astrophysics Data System (ADS)
Chang, Bingguo; Chen, Xiaofei
2018-05-01
Ultrasonography is an important examination for the diagnosis of chronic liver disease. The doctor gives the liver indicators and suggests the patient's condition according to the description of ultrasound report. With the rapid increase in the amount of data of ultrasound report, the workload of professional physician to manually distinguish ultrasound results significantly increases. In this paper, we use the spectral clustering method to cluster analysis of the description of the ultrasound report, and automatically generate the ultrasonic diagnostic diagnosis by machine learning. 110 groups ultrasound examination report of chronic liver disease were selected as test samples in this experiment, and the results were validated by spectral clustering and compared with k-means clustering algorithm. The results show that the accuracy of spectral clustering is 92.73%, which is higher than that of k-means clustering algorithm, which provides a powerful ultrasound-assisted diagnosis for patients with chronic liver disease.
Adaptive kernel regression for freehand 3D ultrasound reconstruction
NASA Astrophysics Data System (ADS)
Alshalalfah, Abdel-Latif; Daoud, Mohammad I.; Al-Najar, Mahasen
2017-03-01
Freehand three-dimensional (3D) ultrasound imaging enables low-cost and flexible 3D scanning of arbitrary-shaped organs, where the operator can freely move a two-dimensional (2D) ultrasound probe to acquire a sequence of tracked cross-sectional images of the anatomy. Often, the acquired 2D ultrasound images are irregularly and sparsely distributed in the 3D space. Several 3D reconstruction algorithms have been proposed to synthesize 3D ultrasound volumes based on the acquired 2D images. A challenging task during the reconstruction process is to preserve the texture patterns in the synthesized volume and ensure that all gaps in the volume are correctly filled. This paper presents an adaptive kernel regression algorithm that can effectively reconstruct high-quality freehand 3D ultrasound volumes. The algorithm employs a kernel regression model that enables nonparametric interpolation of the voxel gray-level values. The kernel size of the regression model is adaptively adjusted based on the characteristics of the voxel that is being interpolated. In particular, when the algorithm is employed to interpolate a voxel located in a region with dense ultrasound data samples, the size of the kernel is reduced to preserve the texture patterns. On the other hand, the size of the kernel is increased in areas that include large gaps to enable effective gap filling. The performance of the proposed algorithm was compared with seven previous interpolation approaches by synthesizing freehand 3D ultrasound volumes of a benign breast tumor. The experimental results show that the proposed algorithm outperforms the other interpolation approaches.
Qiao, Yangzi; Cao, Hua; Zhang, Shusheng; Yin, Hui; Wan, Mingxi
2013-01-01
Ultrasound contrast agents (UCAs) are frequently added into the focused ultrasound field as cavitation nuclei to enhance the therapeutic efficiency. Since their presence will distort the pressure field and make the process unpredictable, comprehension of their behaviors especially the active zone spatial distribution is an important part of better monitoring and using of UCAs. As shell materials can strongly alter the acoustic behavior of UCAs, two different shells coated UCAs, lipid-shelled and polymer-shelled UCAs, in a 1.2 MHz focused ultrasound field were studied by the Sonochemiluminescence (SCL) method and compared. The SCL spatial distribution of lipid-shelled group differed from that of polymer-shelled group. The shell material and the character of focused ultrasound field work together to the SCL distribution, causing the lipid-shelled group to have a maximum SCL intensity in pre-focal region at lower input power than that of polymer-shelled group, and a brighter SCL intensity in post-focal region at high input power. The SCL inactive area of these two groups both increased with the input power. The general behavior of the UCAs can be studied by both the average SCL intensity and the backscatter signals. As polymer-shelled UCAs are more resistant to acoustic pressure, they had a higher destruction power and showed less reactivation than lipid-shelled ones. Copyright © 2012 Elsevier B.V. All rights reserved.
Virtual Guidance Ultrasound: A Tool to Obtain Diagnostic Ultrasound for Remote Environments
NASA Technical Reports Server (NTRS)
Caine,Timothy L.; Martin David S.; Matz, Timothy; Lee, Stuart M. C.; Stenger, Michael B.; Platts, Steven H.
2012-01-01
Astronauts currently acquire ultrasound images on the International Space Station with the assistance of real-time remote guidance from an ultrasound expert in Mission Control. Remote guidance will not be feasible when significant communication delays exist during exploration missions beyond low-Earth orbit. For example, there may be as much as a 20- minute delay in communications between the Earth and Mars. Virtual-guidance, a pre-recorded audio-visual tutorial viewed in real-time, is a viable modality for minimally trained scanners to obtain diagnostically-adequate images of clinically relevant anatomical structures in an autonomous manner. METHODS: Inexperienced ultrasound operators were recruited to perform carotid artery (n = 10) and ophthalmic (n = 9) ultrasound examinations using virtual guidance as their only instructional tool. In the carotid group, each each untrained operator acquired two-dimensional, pulsed, and color Doppler of the carotid artery. In the ophthalmic group, operators acquired representative images of the anterior chamber of the eye, retina, optic nerve, and nerve sheath. Ultrasound image quality was evaluated by independent imaging experts. RESULTS: Eight of the 10 carotid studies were judged to be diagnostically adequate. With one exception the quality of all the ophthalmic images were adequate to excellent. CONCLUSION: Diagnostically-adequate carotid and ophthalmic ultrasound examinations can be obtained by untrained operators with instruction only from an audio/video tutorial viewed in real time while scanning. This form of quick-response-guidance, can be developed for other ultrasound examinations, represents an opportunity to acquire important medical and scientific information for NASA flight surgeons and researchers when trained medical personnel are not present. Further, virtual guidance will allow untrained personnel to autonomously obtain important medical information in remote locations on Earth where communication is
Ultrasound as pretreatment to convective drying of Andean blackberry (Rubus glaucus Benth).
Romero J, Carlos A; Yépez V, Byron D
2015-01-01
In this study, we evaluated the use of ultrasound as a pretreatment for convective drying of Andean blackberry (Rubus glaucus Benth). For this, a Box-Behnken experimental design was used to study the effect of ultrasound vibration amplitude (0-90μm), time of sonication (10-30min) and air temperature (40-60°C) on the retention of antioxidant compounds and on the kinetics of convective drying. The results showed that the antioxidant activity on fruit was reduced as the vibration amplitude and time of sonication increased, while was found that vibration amplitude ultrasound and air drying temperature were the variables that more affect the drying rate of blackberries. The drying rate increased by almost five times when samples were treated with ultrasound at 90μm for 20min. They were then dried using air at 60°C. It is concluded that the application of ultrasound in blackberry processing allows to obtain a dehydrated product with better functional quality and shows to be effective in reducing the time necessary to achieve a given value of moisture during convective drying. Copyright © 2014 Elsevier B.V. All rights reserved.
Guiding tissue regeneration with ultrasound in vitro and in vivo
NASA Astrophysics Data System (ADS)
Dalecki, Diane; Comeau, Eric S.; Raeman, Carol H.; Child, Sally Z.; Hobbs, Laura; Hocking, Denise C.
2015-05-01
Developing new technologies that enable the repair or replacement of injured or diseased tissues is a major focus of regenerative medicine. This paper will discuss three ultrasound technologies under development in our laboratories to guide tissue regeneration both in vitro and in vivo. A critical obstacle in tissue engineering is the need for rapid and effective tissue vascularization strategies. To address this challenge, we are developing acoustic patterning techniques for microvascular tissue engineering. Acoustic radiation forces associated with ultrasound standing wave fields provide a rapid, non-invasive approach to spatially pattern cells in three dimensions without affecting cell viability. Acoustic patterning of endothelial cells leads to the rapid formation of microvascular networks throughout the volumes of three-dimensional hydrogels, and the morphology of the resultant microvessel networks can be controlled by design of the ultrasound field. A second technology under development uses ultrasound to noninvasively control the microstructure of collagen fibers within engineered tissues. The microstructure of extracellular matrix proteins provides signals that direct cell functions critical to tissue regeneration. Thus, controlling collagen microfiber structure with ultrasound provides a noninvasive approach to regulate the mechanical properties of biomaterials and control cellular responses. The third technology employs therapeutic ultrasound to enhance the healing of chronic wounds. Recent studies demonstrate increased granulation tissue thickness and collagen deposition in murine dermal wounds exposed to pulsed ultrasound. In summary, ultrasound technologies offer noninvasive approaches to control cell behaviors and extracellular matrix organization and thus hold great promise to advance tissue regeneration in vitro and in vivo.
The management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust
Peacock, M
2013-01-01
Management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust is described. The organisation and input of various stakeholders and their involvement with ultrasound equipment management and scientific ultrasound is discussed. Two important stakeholders are the Medical Equipment Management Group and the Radiation Safety Steering Committee. The Medical Equipment Management Group has a specific sub-group, the Ultrasound sub-group, and its role is to coordinate the purchase, replacement and quality assurance of ultrasound equipment in the Trust. The Radiation Safety Steering Committee has a non-ionising radiation representative and the role of this committee is to provide corporate assurance that any health and safety issues arising from the use of radiation to either patients, members of the public or staff within the Trust are being effectively managed. The Ultrasound sub-group of the Medical Equipment Management Group has successfully brought together management of all ultrasound equipment within the Trust and is in the process of fulfilling the quality assurance and training milestones set out by the Medical Equipment Management Group. Advice from the Radiation Safety Steering Committee has helped to increase awareness of ultrasound safety and good scanning practice, especially in the case of neonatal ultrasound imaging, within the Trust. In addition, the RSSC has given advice on clinical pathways for patients undergoing ionising radiation imaging while being treated by extra-corporeal shockwave lithotripsy. PMID:27433195
Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo
2018-01-01
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.
Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy
Yoshida, E. J.; Chen, H.; Torres, M. A.; Curran, W. J.; Liu, T.
2011-01-01
Purpose: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study’s purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Methods : Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters—melanin and erythema indices—were used to quantitatively assess skin discoloration. Two ultrasound parameters—skin thickness and Pearson coefficient of the hypodermis—were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Results: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Conclusions: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for
Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.
Yoshida, E J; Chen, H; Torres, M A; Curran, W J; Liu, T
2011-10-01
Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful
2006-01-01
The paper compares the efficiency of infrasound and ultrasound phonophoreses. The efficiency was evaluated on the basis of the rate of radiotracers within the eye after infrasound or ultrasound exposure of the eyeball. The exposure was made after preliminary putting the radiotracer-impregnated application into the bulbar conjunctiva of an animal. Radioactivity was recorded on a Siemens gamma camera in its lifetime. The time course of changes in the radioactivities measured 10, 30, and 60 minutes after termination of exposures strongly suggests its stable increase in the eye exposed to infrasound. At the same time 10 minutes after ultrasound exposure, the increased concentration of a radiotracer in the eye was less than that after infrasound exposure and then it progressively decreased. Thus, having a significant phoretic activity, infrasound, as ultrasound, creates more favorable conditions for long drug storage in the eye.
In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.
Grishenkov, Dmitry; Gonon, Adrian; Janerot-Sjoberg, Birgitta
2015-09-01
Quantification of myocardial perfusion by contrast echocardiography remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled. To contribute toward an improvement, we developed a contrast echocardiographic perfusion imaging platform based on an isolated rat heart coupled to an ultrasound scanner. Perfusion was assessed by using 3 different types of contrast agents: dextran-based Promiten (Meda AB, Solna, Sweden), phospholipid-shelled SonoVue (Bracco Diagnostics, Inc, Princeton, NJ), and polymer-shelled MB-pH5-RT, developed in-house. The myocardial video intensity was monitored over time from contrast agent administration to peak, and 2 characteristic constants were calculated by using an exponential fit: A, representing capillary volume; and β, representing inflow velocity. Acquired experimental evidence demonstrates that the application of all 3 contrast agents allows sonographic estimation of myocardial perfusion in the isolated rat heart. Video intensity maps show that an increase in contrast concentration increases the late-plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to A × β, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by a flowmeter attached to the aortic cannula. The contrast echocardiographic perfusion imaging platform described holds promise for standardized evaluation and optimization of contrast perfusion ultrasound imaging in which real-time inflow curves at low acoustic power semiquantitatively reflect coronary flow. © 2015 by the American Institute of Ultrasound in Medicine.
Ultrasound assisted forward osmosis concentration of fruit juice and natural colorant.
Chanukya, B S; Rastogi, Navin K
2017-01-01
The present study deals with the effect of higher and lower molecular weight compounds present in the feed on concentration polarization during forward osmosis concentration and its mitigation by the application of ultrasound. The effects of ultrasound on transmembrane water flux at different forward osmosis membrane orientations and different model feed solutions consisting of sucrose and pectin have also been evaluated. The feed containing sucrose and pectin subjected towards active layer of the membrane was found to be the most suitable orientation. The application of ultrasound (30kHz) significantly reduced the concentration polarization when the feed contains sucrose concentration up to 5%. Whereas, in case of feed containing 0.5% pectin, the ultrasound was not found to be effective in dislodging the gel layer formation resulting in severe external concentration polarization on the membrane surface. In comparison to the ordinary forward osmosis process, the ultrasound-assisted forward osmosis process resulted in higher water fluxes in case of sweet lime juice as well as rose extract containing anthocyanin. The degradation of rose anthocyanin due to ultrasound was found to be 1.82%. Application of ultrasound was found to be an effective way in mitigating concentration polarization on the forward osmosis membrane resulting in increased flux. Copyright © 2016 Elsevier B.V. All rights reserved.
ASSOCIATIONS BETWEEN ULTRASOUND AND CLINICAL FINDINGS IN 87 CATS WITH URETHRAL OBSTRUCTION.
Nevins, Jonathan R; Mai, Wilfried; Thomas, Emily
2015-01-01
Urethral obstruction is a life-threatening form of feline lower urinary tract disease. Ultrasonographic risk factors for reobstruction have not been previously reported. Purposes of this retrospective cross-sectional study were to describe urinary tract ultrasound findings in cats following acute urethral obstruction and determine whether ultrasound findings were associated with reobstruction. Inclusion criteria were a physical examination and history consistent with urethral obstruction, an abdominal ultrasound including a full evaluation of the urinary system within 24 h of hospitalization, and no cystocentesis prior to ultrasound examination. Medical records for included cats were reviewed and presence of azotemia, hyperkalemia, positive urine culture, and duration of hospitalization were recorded. For medically treated cats with available outcome data, presence of reobstruction was also recorded. Ultrasound images were reviewed and urinary tract characteristics were recorded. A total of 87 cats met inclusion criteria. Common ultrasound findings for the bladder included echogenic urine sediment, bladder wall thickening, pericystic effusion, hyperechoic pericystic fat, and increased urinary echoes; and for the kidneys/ureters included pyelectasia, renomegaly, perirenal effusion, hyperechoic perirenal fat, and ureteral dilation. Six-month postdischarge outcomes were available for 61 medically treated cats and 21 of these cats had reobstruction. No findings were associated with an increased risk of reobstruction. Ultrasonographic perirenal effusion was associated with severe hyperkalemia (P = 0.009, relative risk 5.75, 95% confidence interval [1.54-21.51]). Findings supported the use of ultrasound as an adjunct for treatment planning in cats presented with urethral obstruction but not as a method for predicting risk of reobstruction. © 2015 American College of Veterinary Radiology.
Recent advances in ultrasound-triggered therapy.
Yang, Chaopin; Li, Yue; Du, Meng; Chen, Zhiyi
2018-04-27
As a non-invasive and real-time diagnostic technique, ultrasound has provided a novel strategy for targeted treatment. With the rapid development of ultrasonic technique and ultrasound contrast agents (UCAs), spatiotemporally controllable application of ultrasound with or without UCAs makes it possible for site-specific delivery of therapeutic agents and targeted modulation with minimal side effects, which indicated a promising therapy in clinical use. This review will describe the main mechanism of targeted therapy induced by ultrasound briefly, then focus on the current application of ultrasound mediated targeted therapy in various fields including tumour, cardiovascular disease, central nervous system, skeletal muscle system diseases and stem cells therapy. In addition, ongoing challenges of ultrasound-mediated targeted therapy for further research and its clinical use are reviewed.
NASA Astrophysics Data System (ADS)
Tadayon, Mohammad Amin
Piezoelectric technology is the backbone of most medical ultrasound imaging arrays, however, in scaling the technology to sizes required for high frequency operation (> 20 MHz), it encounters substantial difficulties in fabrication and signal transduction efficiency. These limitations particularly affect the design of intravascular ultrasound (IVUS) imaging probes whose operating frequency can approach 60 MHz. Optical technology has been proposed and investigated for several decades as an alternative approach for high frequency ultrasound transducers. However, to apply this promising technology in guiding clinical operations such as in interventional cardiology, brain surgery, and laparoscopic surgery further raise in the sensitivity is required. Here, in order to achieve the required sensitivity for an intravascular ultrasound imaging probe, we introduce design changes making use of alternative receiver mechanisms. First, we present an air cavity detector that makes use of a polymer membrane for increased mechanical deflection. We have also significantly raised the thin film detector sensitivity by improving its optical characteristics. This can be achieved by inducing a refractive index feature inside the Fabry-Perot resonator that simply creates a waveguide between the two mirrors. This approach eliminates the loss in energy due to diffraction in the cavity, and therefore the Q-factor is only limited by mirror loss and absorption. To demonstrate this optical improvements, a waveguide Fabry-Perot resonator has been fabricated consisting of two dielectric Bragg reflectors with a layer of photosensitive polymer between them. The measured finesse of the fabricated resonator was 692, and the Q-factor was 55000. The fabrication process of this device has been modified to fabricate an ultrasonically testable waveguide Fabry-Perot resonator. By applying this method, we have achieved a noise equivalent pressure of 178 Pa over a bandwidth of 28 MHz or 0.03 Pa/Hz1/2 which
MR-guided Focused Ultrasound for Uterine Fibroids
... Professions Site Index A-Z MR-guided Focused Ultrasound for Uterine Fibroids Magnetic Resonance-guided Focused Ultrasound ( ... are the limitations of MRgFUS? What is Focused Ultrasound of Uterine Fibroids? Magnetic Resonance-guided Focused Ultrasound ( ...
Anterolateral ankle impingement: findings and diagnostic accuracy with ultrasound imaging.
McCarthy, C L; Wilson, D J; Coltman, T P
2008-03-01
The objective was to evaluate the findings and diagnostic accuracy of ultrasound in antero-lateral ankle impingement (ALI) with clinical and arthroscopic correlation. Seventeen elite footballers with chronic ankle pain were referred for ultrasound with a clinical diagnosis of ALI (n = 8) or a control condition (n = 9; lateral mechanical instability, osteochondral defect, intra-articular bodies and osteoarthritis). Ultrasound examination included the antero-lateral gutter for abnormal synovial tissue (synovitic lesion), lateral ligament integrity, tibiotalar joint and osseous spurs of the distal tibia and talus. Ultrasound findings were correlated with subsequent arthroscopic appearance. Ultrasound examination detected a synovitic mass in the antero-lateral gutter in all 8 footballers with clinical ALI (100%) and in 2 patients with a control diagnosis (22%). Arthroscopic correlation of antero-lateral synovitis and fibrosis was present in all 10 cases (100%). The synovitic lesion was seen at ultrasound as a nodular soft tissue mass of mixed echogenicity within the antero-lateral gutter, which extruded anteriorly with manual compression of the distal fibula against the tibia. Increased blood supply was detected using power Doppler imaging in only 1 patient. The synovitic lesion measured >10 mm in its maximum dimension in 7 footballers with clinical ALI and <10 mm in the control group. Additional ultrasound findings in patients with abnormal antero-lateral synovial tissue included an anterior talofibular ligament injury in all patients (n = 10), a tibiotalar joint effusion (n = 6) and osseous spurs (n = 4). Antero-lateral synovitic tissue was accurately identified at ultrasound in the absence of an effusion (n = 4). No synovitic lesion was detected at ultrasound or arthroscopy in the remaining 7 patients with a control diagnosis. Ultrasound is accurate in detecting synovitic lesions within the antero-lateral gutter, demonstrating associated ligamentous injuries and in
Ethical analysis of non-medical fetal ultrasound.
Leung, John Lai Yin; Pang, Samantha Mei Che
2009-09-01
Obstetric ultrasound is the well-recognized prenatal test used to visualize and determine the condition of a pregnant woman and her fetus. Apart from the clinical application, some businesses have started promoting the use of fetal ultrasound machines for nonmedical reasons. Non-medical fetal ultrasound (also known as 'keepsake' ultrasound) is defined as using ultrasound to view, take a picture, or determine the sex of a fetus without a medical indication. Notwithstanding the guidelines and warnings regarding ultrasound safety issued by governments and professional bodies, the absence of scientifically proven physical harm to fetuses from this procedure seems to provide these businesses with grounds for rapid expansion. However, this argument is too simplistic because current epidemiological evidence is not synchronous with advancing ultrasound technology. As non-medical fetal ultrasound has aroused very significant public attention, a thorough ethical analysis of this topic is essential. Using a multifaceted approach, we analyse the ethical perspective of non-medical fetal ultrasound in terms of the expectant mother, the fetus and health professionals. After applying four major theories of ethics and principles (the precautionary principle; theories of consequentialism and impartiality; duty-based theory; and rights-based theories), we conclude that obstetric ultrasound practice is ethically justifiable only if the indication for its use is based on medical evidence. Non-medical fetal ultrasound can be considered ethically unjustifiable. Nevertheless, the ethical analysis of this issue is time dependent owing to rapid advancements in ultrasound technology and the safety issue. The role of health professionals in ensuring that obstetric ultrasound is an ethically justifiable practice is also discussed.
Molecular Ultrasound Imaging for the Detection of Neural Inflammation
NASA Astrophysics Data System (ADS)
Volz, Kevin R.
performed while targeting three early inflammatory markers (P-selectin, VCAM-1, ICAM-1). Imaging protocols and outcome measures of previous TCEUS investigations of inflammation were replicated to aid in comparisons of outcomes. Signal intensity data was used to generate time intensity curves for qualitative and quantitative analysis of contrast agent temporal behavior. A proof of principle study established preclinical evidence to support the ability of TCEUS to detect acute neural inflammation. Substantial increases in signal intensities were observed while targeting inflammatory markers compared to controls. Further investigations consisted of examining molecular ultrasound sensitivity, and were accomplished by examining targeted contrast agent dosing parameters, and the ability of TCEUS to longitudinally evaluate neural inflammation. Qualitative analysis of TCEUS imaging performed with both administered doses revealed marked increases in signal intensities during acute inflammation, where inflammatory marker expression was presumably at its highest. This was in comparison to measures obtained in the absence of, and during, chronic inflammation. This research contributes much needed empirical evidence to the molecular ultrasound body of literature, and represents the first steps towards advancing this TCEUS application to clinical practice. Future studies are necessary to further these findings and effectively build upon this evidence. Increasing evidence of TCEUS use for the detection of neural inflammation will aid in its eventual clinical translation, where it will likely have a positive impact on patient care.
Release of indomethacin from ultrasound dry granules containing lactose-based excipients.
Cavallari, Cristina; Albertini, Beatrice; Rodriguez, Lorenzo; Rabasco, Antonio M; Fini, Adamo
2005-01-20
Physical mixtures were prepared containing indomethacin and beta-lactose and alpha-lactose-based excipients (Ludipress and Cellactose). The mixtures were compacted with the aid of ultrasound, obtaining tablets, which were milled and sieved. Granules thus obtained were examined by optical microscopy and differential scanning calorimetry. The intense yellow color of the granules and the absence of indomethacin peak in thermograms suggest important modifications of indomethacin physical state; the drug thus modified appears to be spread on the excipient particle surface as a thin film, giving a lustrous appearance. No influence of ultrasound was observed on phase transition concerning lactose; only loss of water was important under high energy ultrasound. Dissolution profiles suggest an increased release of the drug from the systems treated with ultrasound at high energy, with respect to a traditional compaction; while no difference could be evidenced among the three excipients that, however, appear all suitable for this ultrasound-aided direct compression process.
In situ formation deposited ZnO nanoparticles on silk fabrics under ultrasound irradiation.
Khanjani, Somayeh; Morsali, Ali; Joo, Sang W
2013-03-01
Deposition of zinc(II) oxide (ZnO) nanoparticles on the surface of silk fabrics was prepared by sequential dipping steps in alternating bath of potassium hydroxide and zinc nitrate under ultrasound irradiation. This coating involves in situ generation and deposition of ZnO in a one step. The effects of ultrasound irradiation, concentration and sequential dipping steps on growth of the ZnO nanoparticles have been studied. Results show a decrease in the particles size as increasing power of ultrasound irradiation. Also, increasing of the concentration and sequential dipping steps increase particle size. The physicochemical properties of the nanoparticles were determined by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX). Copyright © 2012 Elsevier B.V. All rights reserved.
Kim, Yeoun Jae; Seo, Jong Hyun; Kim, Hong Rae; Kim, Kwang Gi
2017-06-01
Clinicians who frequently perform ultrasound scanning procedures often suffer from musculoskeletal disorders, arthritis, and myalgias. To minimize their occurrence and to assist clinicians, ultrasound scanning robots have been developed worldwide. Although, to date, there is still no commercially available ultrasound scanning robot, many control methods have been suggested and researched. These control algorithms are either image based or force based. If the ultrasound scanning robot control algorithm was a combination of the two algorithms, it could benefit from the advantage of each one. However, there are no existing control methods for ultrasound scanning robots that combine force control and image analysis. Therefore, in this work, a control algorithm is developed for an ultrasound scanning robot using force feedback and ultrasound image analysis. A manipulator-type ultrasound scanning robot named 'NCCUSR' is developed and a control algorithm for this robot is suggested and verified. First, conventional hybrid position-force control is implemented for the robot and the hybrid position-force control algorithm is combined with ultrasound image analysis to fully control the robot. The control method is verified using a thyroid phantom. It was found that the proposed algorithm can be applied to control the ultrasound scanning robot and experimental outcomes suggest that the images acquired using the proposed control method can yield a rating score that is equivalent to images acquired directly by the clinicians. The proposed control method can be applied to control the ultrasound scanning robot. However, more work must be completed to verify the proposed control method in order to become clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
High prevalence of all complex Segond avulsion using ultrasound imaging.
Klos, Burt; Scholtes, Marlon; Konijnenberg, Stephan
2017-04-01
The aim of this study was to determine the prevalence of a Segond avulsion fractures in acute ACL tears with ultrasound and to investigate whether other injuries can predict the avulsion. One hundred thirty-eight ultrasound analyses of acute knee trauma were collected and scored for diagnosed injuries. The reports of patients with an ACL tear (N = 87) were evaluated to determine possible increased prevalence of Segond avulsion fracture with ultrasound. The associations between the diagnosed injuries and presence of a Segond avulsion were scored. The sports carried out at the time of injury were evaluated as possible prognostic factor. In 25/87 (29%) of the patients with an ACL tear, a Segond avulsion was observed in ultrasound. Lateral femoral condyle (LFC) impaction showed the strongest individual association with a Segond avulsion and was the best predicting variable. LFC impaction, sustained during low-risk pivoting sport, shows a stronger association with a Segond avulsion, as compared to LFC impaction sustained during high-risk pivoting sports. Ultrasound shows a higher prevalence of Segond avulsions as literature shows with MRI or radiography. LFC impaction is the best variable in predicting this type of avulsion. Ultrasound examination should be considered, if this fracture was not diagnosed with MRI or radiographic analysis. IV.
Steinkohl, F; Luger, A; Bektic, J; Aigner, F
2017-08-01
Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.
Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong
2014-01-01
Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.
NASA Astrophysics Data System (ADS)
Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong
2014-01-01
Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.
Evaluation of an Obstetric Ultrasound Curriculum for Midwives in Liberia.
Bentley, Suzanne; Hexom, Braden; Nelson, Bret P
2015-09-01
Point-of-care ultrasound is an effective tool for clinical decision making in low- and middle-income countries, but lack of trained providers is a barrier to its utility in these settings. In Liberia, given that midwives provide most prenatal care, it is hypothesized that training them in prenatal ultrasound through an intensive condensed training course is both feasible and practical. This quantitative prospective study of preobservational and postobservational assessment evaluated a 1-week ultrasound curriculum consisting of 4 modules, each comprising a didactic component, a practical session, and supervised patient encounters. A knowledge-based pretest and presurvey addressing prior use and comfort were administered. At the intervention conclusion, identical posttests and postsurveys were administered with an objective structured clinical examination (OSCE). The test, survey, and OSCE were repeated after 1 year. All scores and responses were tabulated, and qualitative analysis with paired t tests was performed. Thirty-one midwives underwent intervention and written evaluation, with 14 followed up at 1 year. Seventeen underwent the OSCE, with 8 retained at 1 year. There was a significant increase between pretest and immediate and 1-year posttest scores (36.6% versus 90% and 66%; P < .001) but no difference between immediate and 1-year posttest scores (90% versus 66%; P > .05). Average overall comfort using ultrasound increased from presurvey to immediate postsurvey scores (from 1.8 to 3.8; P< .001) and remained higher at the 1-year postsurvey (1.8 to 3.4; P< .05). Overall OSCE scores remained high from immediately after the OSCE to 1 year after the OSCE (78% to 55%; P > .05). Midwives in Liberia had very low baseline knowledge and comfort using ultrasound. A 1-week curriculum increased both short- and long-term knowledge and comfort and led to adequate overall OSCE scores that were retained at 1 year. © 2015 by the American Institute of Ultrasound in Medicine.
Yu, Hongchi; Gao, Min; Ma, Yunlong; Wang, Lijuan; Shen, Yang; Liu, Xiaoheng
2018-05-01
angiogenesis plays an important role in the development and progression of tumors, and it involves a series of signaling pathways contributing to the migration of endothelial cells for vascularization and to the invasion of cancer cells for secondary tumor formation. Among these pathways, the focal adhesion kinase (FAK) signaling cascade has been implicated in a variety of human cancers in connection with cell adhesion and migration events leading to tumor angiogenesis, metastasis and invasion. Therefore, the inhibition of FAK in endothelial and/or cancer cells is a potential target for anti‑angiogenic therapy. In the present study, a small‑molecule FAK inhibitor, 1,2,4,5-benzenetetramine tetrahydrochloride (Y15), was used to study the effects of FAK inhibition on the adhesion and migration behaviors of vascular endothelial cells (VECs) and human hepatoblastoma cells. Furthermore, the time-dependent differences in proteins associated with the integrin-mediated FAK/Rho GTPases signaling pathway within 2 h were examined. The results indicated that the inhibition of FAK significantly decreased the migration ability of VECs and human hepatoblastoma cells in a dose-dependent manner. Inhibition of FAK promoted cell detachment by decreasing the expression of focal adhesion components, and blocked cell motility by reducing the level of Rho GTPases. However, the expression of crucial proteins involved in integrin-induced signaling in two cell lines exhibited a time-dependent difference with increased duration of FAK inhibitor treatment, suggesting different mechanisms of FAK-mediated cell migration behavior. These results suggest that the mechanism underlying FAK-mediated adhesion and migration behavior differs among various cells, which is expected to provide evidence for future FAK therapy targeted against tumor angiogenesis.
Ultrafast Ultrasound Imaging With Cascaded Dual-Polarity Waves.
Zhang, Yang; Guo, Yuexin; Lee, Wei-Ning
2018-04-01
Ultrafast ultrasound imaging using plane or diverging waves, instead of focused beams, has advanced greatly the development of novel ultrasound imaging methods for evaluating tissue functions beyond anatomical information. However, the sonographic signal-to-noise ratio (SNR) of ultrafast imaging remains limited due to the lack of transmission focusing, and thus insufficient acoustic energy delivery. We hereby propose a new ultrafast ultrasound imaging methodology with cascaded dual-polarity waves (CDWs), which consists of a pulse train with positive and negative polarities. A new coding scheme and a corresponding linear decoding process were thereby designed to obtain the recovered signals with increased amplitude, thus increasing the SNR without sacrificing the frame rate. The newly designed CDW ultrafast ultrasound imaging technique achieved higher quality B-mode images than coherent plane-wave compounding (CPWC) and multiplane wave (MW) imaging in a calibration phantom, ex vivo pork belly, and in vivo human back muscle. CDW imaging shows a significant improvement in the SNR (10.71 dB versus CPWC and 7.62 dB versus MW), penetration depth (36.94% versus CPWC and 35.14% versus MW), and contrast ratio in deep regions (5.97 dB versus CPWC and 5.05 dB versus MW) without compromising other image quality metrics, such as spatial resolution and frame rate. The enhanced image qualities and ultrafast frame rates offered by CDW imaging beget great potential for various novel imaging applications.
Low-frequency quantitative ultrasound imaging of cell death in vivo
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J.
Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicatedmore » significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r{sup 2}= 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant
Variable Access to Immediate Bedside Ultrasound in the Emergency Department
Talley, Brad E.; Ginde, Adit A.; Raja, Ali S.; Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A.
2011-01-01
Objective: Use of bedside emergency department (ED) ultrasound has become increasingly important for the clinical practice of emergency medicine (EM). We sought to evaluate differences in the availability of immediate bedside ultrasound based on basic ED characteristics and physician staffing. Methods: We surveyed ED directors in all 351 EDs in Colorado, Georgia, Massachusetts, and Oregon between January and April 2009. We assessed access to bedside ED ultrasound by the question: “Is bedside ultrasound available immediately in the ED?” ED characteristics included location, visit volume, admission rate, percent uninsured, total emergency physician full-time equivalents and proportion of EM board-certified (BC) or EM board-eligible (BE) physicians. Data analysis used chi-square tests and multivariable logistical regression to compare differences in access to bedside ED ultrasound by ED characteristics and staffing. Results: We received complete responses from 298 (85%) EDs. Immediate access to bedside ultrasound was available in 175 (59%) EDs. ED characteristics associated with access to bedside ultrasound were: location (39% for rural vs. 71% for urban, P<0.001); visit volume (34% for EDs with low volume [<1 patient/hour] vs. 79% for EDs with high volume [≥3 patients/hour], P<0.001); admission rate (39% for EDs with low [0–10%] admission rates vs. 84% for EDs with high [>20%] rates, P<0.001); and EM BC/BE physicians (26% for EDs with a low percentage [0–20%] vs.74% for EDs with a high percentage [≥80%], P<0.001). Conclusion: U.S. EDs differ significantly in their access to immediate bedside ultrasound. Smaller, rural EDs and those staffed by fewer EM BC/BE physicians more frequently lacked access to immediate bedside ultrasound in the ED. PMID:21691479
Ultrasound in twin pregnancies.
Morin, Lucie; Lim, Kenneth
2011-06-01
technologies) should have first trimester ultrasound performed. (II-2A) 2. Every attempt should be made to determine and report amnionicity and chorionicity when a twin pregnancy is identified. (II-2A) 3. Although the accuracy in confirmation of gestational age at the first and second trimester is comparable, dating should be done with first trimester ultrasound. (II-2A) 4. Beyond the first trimester, it is suggested that a combination of parameters rather than a single parameter should be used to confirm gestational age. (II-2C) 5. When twin pregnancy is the result of in vitro fertilization, accurate determination of gestational age should be made from the date of embryo transfer. (II-1A) 6. There is insufficient evidence to make a recommendation of which fetus (when discordant for size) to use to date a twin pregnancy. However, to avoid missing a situation of early intrauterine growth restriction in one twin, most experts agree that the clinician may consider dating pregnancy using the larger fetus. (III-C) 7. In twin pregnancies, aneuploidy screening using nuchal transluscency measurements should be offered. (II-2B) 8. Detailed ultrasound examination to screen for fetal anomalies should be offered, preferably between 18 and 22 weeks' gestation, in all twin pregnancies. (II-2B) 9. When ultrasound is used to screen for preterm birth in a twin gestation, endovaginal ultrasound measurement of the cervical length should be performed. (II-2A) 10. Increased fetal surveillance should be considered when there is either growth restriction diagnosed in one twin or significant growth discordance. (II-2A) 11. Umbilical artery Doppler should not be routinely offered in uncomplicated twin pregnancies. (I-E) 12. For defining oligohydramnios and polyhydramnios, the ultrasonographer should use the deepest vertical pocket in either sac: oligohydramnios when < 2 cm and polyhydramnios when > 8 cm. (II-2B).
Liu, Spencer S; John, Raymond S
2010-01-01
Ultrasound guidance for regional anesthesia has increased in popularity. However, the cost of ultrasound versus nerve stimulator guidance is controversial, as multiple and varying cost inputs are involved. Sensitivity analysis allows modeling of different scenarios and determination of the relative importance of each cost input for a given scenario. We modeled cost per patient of ultrasound versus nerve stimulator using single-factor sensitivity analysis for 4 different clinical scenarios designed to span the expected financial impact of ultrasound guidance. The primary cost factors for ultrasound were revenue from billing for ultrasound (85% of variation in final cost), number of patients examined per ultrasound machine (10%), and block success rate (2.6%). In contrast, the most important input factors for nerve stimulator were the success rate of the nerve stimulator block (89%) and the amount of liability payout for failed airway due to rescue general anesthesia (9%). Depending on clinical scenario, ultrasound was either a profit or cost center. If revenue is generated, then ultrasound-guided blocks consistently become a profit center regardless of clinical scenario in our model. Without revenue, the clinical scenario dictates the cost of ultrasound. In an ambulatory setting, ultrasound is highly competitive with nerve stimulator and requires at least a 96% success rate with nerve stimulator before becoming more expensive. In a hospitalized scenario, ultrasound is consistently more expensive as the uniform use of general anesthesia and hospitalization negate any positive cost effects from greater efficiency with ultrasound.
Lin, Kao-Han; Young, Sun-Yi; Hsu, Ming-Chuan; Chan, Hsu; Chen, Yung-Yaw; Lin, Win-Li
2008-01-01
In this study, we developed a focused ultrasound (FUS) thermal therapy system with ultrasound image guidance and thermocouple temperature measurement feedback. Hydraulic position devices and computer-controlled servo motors were used to move the FUS transducer to the desired location with the measurement of actual movement by linear scale. The entire system integrated automatic position devices, FUS transducer, power amplifier, ultrasound image system, and thermocouple temperature measurement into a graphical user interface. For the treatment procedure, a thermocouple was implanted into a targeted treatment region in a tissue-mimicking phantom under ultrasound image guidance, and then the acoustic interference pattern formed by image ultrasound beam and low-power FUS beam was employed as image guidance to move the FUS transducer to have its focal zone coincident with the thermocouple tip. The thermocouple temperature rise was used to determine the sonication duration for a suitable thermal lesion as a high power was turned on and ultrasound image was used to capture the thermal lesion formation. For a multiple lesion formation, the FUS transducer was moved under the acoustic interference guidance to a new location and then it sonicated with the same power level and duration. This system was evaluated and the results showed that it could perform two-dimensional motion control to do a two-dimensional thermal therapy with a small localization error 0.5 mm. Through the user interface, the FUS transducer could be moved to heat the target region with the guidance of ultrasound image and acoustic interference pattern. The preliminary phantom experimental results demonstrated that the system could achieve the desired treatment plan satisfactorily.
Ghodbane, Houria; Hamdaoui, Oualid
2009-06-01
In this work, the sonolytic degradation of an anthraquinonic dye, C.I. Acid Blue 25 (AB25), in aqueous phase using high frequency ultrasound waves (1700kHz) for an acoustic power of 14W was investigated. The sonochemical efficiency of the reactor was evaluated by potassium iodide dosimeter, Fricke reaction and hydrogen peroxide production yield. The three investigated methods clearly show the production of oxidizing species during sonication and well reflect the sonochemical effects of high frequency ultrasonic irradiation. The effect of operational conditions such as the initial AB25 concentration, solution temperature and pH on the degradation of AB25 was studied. Additionally, the influence of addition of salts on the degradation of dye was examined. The rate of AB25 degradation was dependent on initial dye concentration, pH and temperature. Addition of salts increased the degradation of dye. Experiments conducted using distilled and natural waters demonstrated that the degradation was more efficient in the natural water compared to distilled water. To increase the efficiency of AB25 degradation, experiments combining ultrasound with Fe(II) or H(2)O(2) were conducted. Fe(II) induced the dissociation of ultrasonically produced hydrogen peroxide, leading to additional OH radicals which enhance the degradation of dye. The combination of ultrasound with hydrogen peroxide looks to be a promising option to increase the generation of free radicals. The concentration of hydrogen peroxide plays a crucial role in deciding the extent of enhancement obtained for the combined process. The results of the present work indicate that ultrasound/H(2)O(2) and ultrasound/Fe(II) processes are efficient for the degradation of AB25 in aqueous solutions by high frequency ultrasonic irradiation.
Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.
2012-01-01
SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588
Ultrasound elastography: the new frontier in direct measurement of muscle stiffness.
Brandenburg, Joline E; Eby, Sarah F; Song, Pengfei; Zhao, Heng; Brault, Jeffrey S; Chen, Shigao; An, Kai-Nan
2014-11-01
The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Ultrasound Elastography: The New Frontier in Direct Measurement of Muscle Stiffness
Brandenburg, Joline E.; Eby, Sarah F.; Song, Pengfei; Zhao, Heng; Brault, Jeffrey S.; Chen, Shigao; An, Kai-Nan
2014-01-01
The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research. PMID:25064780
Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.
Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y
1998-12-01
Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.
Oelze, Michael L; Mamou, Jonathan
2016-02-01
Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation, and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years, QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient (BSC), estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter (ESD) and the effective acoustic concentration (EAC) of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on
Oelze, Michael L.; Mamou, Jonathan
2017-01-01
Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging techniques can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient, estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter and the effective acoustic concentration of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on clinical
Unpowered wireless ultrasound tomography system
NASA Astrophysics Data System (ADS)
Zahedi, Farshad; Huang, Haiying
2016-04-01
In this paper, an unpowered wireless ultrasound tomography system is presented. The system consists of two subsystems; the wireless interrogation unit (WIU) and three wireless nodes installed on the structure. Each node is designed to work in generation and sensing modes, but operates at a specific microwave frequency. Wireless transmission of the ultrasound signals between the WIU and the wireless nodes is achieved by converting ultrasound signals to microwave signals and vice versa, using a microwave carrier signal. In the generation mode, both a carrier signal and an ultrasound modulated microwave signal are transmitted to the sensor nodes. Only the node whose operating frequency matches the carrier signal will receive these signals and demodulate them to recover the original ultrasound signal. In the sensing mode, a microwave carrier signal with two different frequency components matching the operating frequencies of the sensor nodes is broadcasted by the WIU. The sensor nodes, in turn, receive the corresponding carrier signals, modulate it with the ultrasound sensing signal, and wirelessly transmit the modulated signal back to the WIU. The demodulation of the sensing signals is performed in the WIU using a digital signal processing. Implementing a software receiver significantly reduces the complexity and the cost of the WIU. A wireless ultrasound tomography system is realized by interchanging the carrier frequencies so that the wireless transducers can take turn to serve as the actuator and sensors.
Unusual Applications of Ultrasound in Industry
NASA Astrophysics Data System (ADS)
Keilman, George
The application of physical acoustics in industry has been accelerated by increased understanding of the physics of industrial processes, coupled with rapid advancements in transducers, microelectronics, data acquisition, signal processing, and related software fields. This has led to some unusual applications of ultrasound to improve industrial processes.
Elasticity-based three dimensional ultrasound real-time volume rendering
NASA Astrophysics Data System (ADS)
Boctor, Emad M.; Matinfar, Mohammad; Ahmad, Omar; Rivaz, Hassan; Choti, Michael; Taylor, Russell H.
2009-02-01
Volumetric ultrasound imaging has not gained wide recognition, despite the availability of real-time 3D ultrasound scanners and the anticipated potential of 3D ultrasound imaging in diagnostic and interventional radiology. Their use, however, has been hindered by the lack of real-time visualization methods that are capable of producing high quality 3D rendering of the target/surface of interest. Volume rendering is a known visualization method, which can display clear surfaces out of the acquired volumetric data, and has an increasing number of applications utilizing CT and MRI data. The key element of any volume rendering pipeline is the ability to classify the target/surface of interest by setting an appropriate opacity function. Practical and successful real-time 3D ultrasound volume rendering can be achieved in Obstetrics and Angio applications where setting these opacity functions can be done rapidly, and reliably. Unfortunately, 3D ultrasound volume rendering of soft tissues is a challenging task due to the presence of significant amount of noise and speckle. Recently, several research groups have shown the feasibility of producing 3D elasticity volume from two consecutive 3D ultrasound scans. This report describes a novel volume rendering pipeline utilizing elasticity information. The basic idea is to compute B-mode voxel opacity from the rapidly calculated strain values, which can also be mixed with conventional gradient based opacity function. We have implemented the volume renderer using GPU unit, which gives an update rate of 40 volume/sec.
Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.
Colen, Rivka R; Sahnoune, Iman; Weinberg, Jeffrey S
2017-10-01
Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules. Copyright © 2017 Elsevier Inc. All rights reserved.
Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D
2014-06-01
Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Ultrasound as an Adjunct to Mammography for Breast Cancer Screening: A Health Technology Assessment
Nikitovic-Jokic, Milica; Tu, Hong Anh; Palimaka, Stefan; Higgins, Caroline; Holubowich, Corinne
2016-01-01
Background Screening with mammography can detect breast cancer early, before clinical symptoms appear. Some cancers, however, are not captured with mammography screening alone. Ultrasound has been suggested as a safe adjunct screening tool that can detect breast cancers missed on mammography. We investigated the benefits, harms, cost-effectiveness, and cost burden of ultrasound as an adjunct to mammography compared with mammography alone for screening women at average risk and at high risk for breast cancer. Methods We searched Ovid MEDLINE, Ovid Embase, EBM Reviews, and the NHS Economic Evaluation Database, from January 1998 to June 2015, for evidence of effectiveness, harms, diagnostic accuracy, and cost-effectiveness. Only studies evaluating the use of ultrasound as an adjunct to mammography in the specified populations were included. We also conducted a cost analysis to estimate the costs in Ontario over the next 5 years to fund ultrasound as an adjunct to mammography in breast cancer screening for high-risk women who are contraindicated for MRI, the current standard of care to supplement mammography. Results No studies in average-risk women met the inclusion criteria of the clinical review. We included 5 prospective, paired cohort studies in high-risk women, 4 of which were relevant to the Ontario context. Adjunct ultrasound identified between 2.3 and 5.9 additional breast cancers per 1,000 screens. The average pooled sensitivity of mammography and ultrasound was 53%, a statistically significant increase relative to mammography alone (absolute increase 13%; P < .05). The average pooled specificity of the combined test was 96%, an absolute increase in the false-positive rate of 2% relative to mammography screening alone. The GRADE for this body of evidence was low. Additional annual costs of using breast ultrasound as an adjunct to mammography for high-risk women in Ontario contraindicated for MRI would range from $15,500 to $30,250 in the next 5 years
Nomura, Jason T; Sierzenski, Paul R; Nace, Jason E; Bollinger, Melissa
2008-07-01
Use of ultrasound guidance for Central Venous Catheter insertion has been associated with decreased complications and increased success rates. Previous reports show low rates of use among physicians. Evaluation of the frequency of Ultrasound Guidance use for Central Venous Catheter insertion among residents at a teaching institution. A cross sectional electronic survey of resident physicians at a tertiary care teaching hospital was conducted to evaluate use of Ultrasound Guidance for Central Venous Catheterization. Assessment included self reported frequency of ultrasound guidance use, and volume of central venous catheter placement. Attitudes toward the use of ultrasound were assessed using Likert scales. There is a high rate. over 90%, of ultrasound guidance use for Internal Jugular central venous catheters among residents. The majority of residents use sterile real-time imaging with a single operator with a reported success rate greater then 80%. Resident use of ultrasound guidance for Internal Jugular central venous catheter insertion can be much higher than previously reported in the literature.
The role of ultrasound guidance in pediatric caudal block
Erbüyün, Koray; Açıkgöz, Barış; Ok, Gülay; Yılmaz, Ömer; Temeltaş, Gökhan; Tekin, İdil; Tok, Demet
2016-01-01
Objectives: To compare the time interval of the procedure, possible complications, post-operative pain levels, additional analgesics, and nurse satisfaction in ultrasonography-guided and standard caudal block applications. Methods: This retrospective study was conducted in Celal Bayar University Hospital, Manisa, Turkey, between January and December 2014, included 78 pediatric patients. Caudal block was applied to 2 different groups; one with ultrasound guide, and the other using the standard method. Results: The time interval of the procedure was significantly shorter in the standard application group compared with ultrasound-guided group (p=0.020). Wong-Baker FACES Pain Rating Scale values obtained at the 90th minute was statistically lower in the standard application group compared with ultrasound-guided group (p=0.035). No statistically significant difference was found on the other parameters between the 2 groups. The shorter time interval of the procedure at standard application group should not be considered as a distinctive mark by the pediatric anesthesiologists, because this time difference was as short as seconds. Conclusion: Ultrasound guidance for caudal block applications would neither increase nor decrease the success of the treatment. However, ultrasound guidance should be needed in cases where the detection of sacral anatomy is difficult, especially by palpations. PMID:26837396
Synthetic aperture imaging in ultrasound calibration
NASA Astrophysics Data System (ADS)
Ameri, Golafsoun; Baxter, John S. H.; McLeod, A. Jonathan; Jayaranthe, Uditha L.; Chen, Elvis C. S.; Peters, Terry M.
2014-03-01
Ultrasound calibration allows for ultrasound images to be incorporated into a variety of interventional applica tions. Traditional Z- bar calibration procedures rely on wired phantoms with an a priori known geometry. The line fiducials produce small, localized echoes which are then segmented from an array of ultrasound images from different tracked probe positions. In conventional B-mode ultrasound, the wires at greater depths appear blurred and are difficult to segment accurately, limiting the accuracy of ultrasound calibration. This paper presents a novel ultrasound calibration procedure that takes advantage of synthetic aperture imaging to reconstruct high resolution ultrasound images at arbitrary depths. In these images, line fiducials are much more readily and accu rately segmented, leading to decreased calibration error. The proposed calibration technique is compared to one based on B-mode ultrasound. The fiducial localization error was improved from 0.21mm in conventional B-mode images to 0.15mm in synthetic aperture images corresponding to an improvement of 29%. This resulted in an overall reduction of calibration error from a target registration error of 2.00mm to 1.78mm, an improvement of 11%. Synthetic aperture images display greatly improved segmentation capabilities due to their improved resolution and interpretability resulting in improved calibration.
Renuka Devi, K; Raja, A; Srinivasan, K
2015-05-01
For the first time, the effect of ultrasound in the diagnostic frequency range of 1-10 MHz on the nucleation and growth characteristics of glycine has been explored. The investigation employing the ultrasonic interferometer was carried out at a constant insonation time over a wide range of relative supersaturation from σ=-0.09 to 0.76 in the solution. Ultrasound promotes only α nucleation and completely inhibits both the β and γ nucleation in the system. The propagation of ultrasound assisted mass transport facilitates nucleation even at very low supersaturation levels in the solution. The presence of ultrasound exhibits a profound effect on nucleation and growth characteristics in terms of decrease in induction period, increase in nucleation rate and decrease in crystal size than its absence in the solution. With an increase in the frequency of ultrasound, a further decrease in induction period, increase in nucleation rate and decrease in the size of the crystal is noticed even at the same relative supersaturation levels. The increase in the nucleation rate explains the combined dominating effects of both the ultrasound frequency and the supersaturation in the solution. Analytically, the nucleation parameters of the nucleated polymorph have been deduced at different ultrasonic frequencies based on the classical nucleation theory and correlations with the experimental results have been obtained. Structural affirmation of the nucleated polymorph has been ascertained by powder X-ray diffraction. Copyright © 2014 Elsevier B.V. All rights reserved.
Holistic ultrasound in trauma: An update.
Saranteas, Theodosios; Mavrogenis, Andreas F
2016-10-01
Holistic ultrasound is a total body examination using an ultrasound device aiming to achieve immediate patient care and decision making. In the setting of trauma, it is one of the most fundamental components of care of the injured patients. Ground-breaking imaging software allows physicians to examine various organs thoroughly, recognize imaging signs early, and potentially foresee the onset or the possible outcome of certain types of injuries. Holistic ultrasound can be performed on a routine basis at the bedside of the patients, at admission and during the perioperative period. Trauma care physicians should be aware of the diagnostic and guidance benefits of ultrasound and should receive appropriate training for the optimal management of their patients. In this paper, the findings of holistic ultrasound in trauma patients are presented, with emphasis on the lungs, heart, cerebral circulation, abdomen, and airway. Additionally, the benefits of ultrasound imaging in interventional anaesthesia techniques such as ultrasound-guided peripheral nerve blocks and central vein catheterization are described. Copyright © 2016 Elsevier Ltd. All rights reserved.
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.
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
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
Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.
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
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
Synergistic advances in diagnostic and therapeutic medical ultrasound
NASA Astrophysics Data System (ADS)
Lizzi, Frederic L.
2003-04-01
Significant advances are more fully exploiting ultrasound's potential for noninvasive diagnosis and treatment. Therapeutic systems employ intense focused beams to thermally kill cancer cells in, e.g., prostate; to stop bleeding; and to treat specific diseases (e.g., glaucoma). Diagnostic ultrasound techniques can quantitatively image an increasingly broad spectrum of physical tissue attributes. An exciting aspect of this progress is the emerging synergy between these modalities. Advanced diagnostic techniques may contribute at several stages in therapy. For example, treatment planning for small ocular tumors uses 50-MHz, 3-D ultrasonic images with 0.05-mm resolution. Thermal simulations employ these images to evaluate desired and undesired effects using exposure stategies with specially designed treatment beams. Therapy beam positioning can use diagnostic elastography to sense tissue motion induced by radiation pressure from high-intensity treatment beams. Therapy monitoring can sense lesion formation using elastography motion sensing (to detect the increased stiffness in lesions); harmonic imaging (to sense altered nonlinear properties); and spectrum analysis images (depicting changes in the sizes, concentration, and configuration of sub-resolution structures.) Experience from these applications will greatly expand the knowledge of acoustic phenomena in living tissues and should lead to further advances in medical ultrasound.
Thoracic ultrasound-assisted selection for pleural biopsy with Abrams needle.
Botana-Rial, Maribel; Leiro-Fernández, Virginia; Represas-Represas, Cristina; González-Piñeiro, Ana; Tilve-Gómez, Amara; Fernández-Villar, Alberto
2013-11-01
Closed pleural biopsy (CPB) in patients with malignant pleural effusion is less sensitive than cytology. Ultrasound-assisted CPB allows biopsies to be performed in the lower thoracic parietal pleura, where secondary spread from pleural metastases is initially more likely to be found. We analyzed whether choosing the point of entry for CPB with thoracic ultrasound assistance influences the diagnostic yield in malignant pleural effusion. This prospective study included patients who underwent CPB performed by an experienced pulmonologist in 2008-2010 (group A) and thoracic ultrasound was used to select the biopsy site. The results were compared with a historical series of CPB performed by the same pulmonologist without the assistance of thoracic ultrasound (group B). An Abrams needle was used in all cases. We analyzed the obtaining of pleural tissue and the diagnostic yield. We included 114 CPBs from group A (23% tuberculous pleural effusion, 27% malignant pleural effusion) and 67 CPBs from group B (24% tuberculous pleural effusion, 30% malignant pleural effusion) (P = .70). Pleural tissue was obtained in 96.5% of the group A CPBs and 89.6% of the group B CPBs (P = .05). The diagnostic yields of CPB for tuberculous pleural effusion and malignant pleural effusion in group A were 89.5% and 77.4%, respectively, and 91.7% and 60%, respectively, in group B (P = .80 for tuberculous pleural effusion, and P = .18 for malignant pleural effusion). Selecting the point of entry for CPB using thoracic ultrasound increases the likelihood of obtaining pleural tissue and the diagnostic yield, but without statistical significance. We recommend ultrasound-assisted CPB to investigate pleural effusion, since the diagnostic yield of a pleural biopsy with an Abrams needle increased by > 17% in subjects with malignant pleural effusion.
Ultrasound-guided peripheral nerve blockade.
Chin, Ki Jinn; Chan, Vincent
2008-10-01
The use of ultrasound for peripheral nerve blockade is becoming popular. Although the feasibility of ultrasound-guided nerve blockade is now clear, it is uncertain at this time whether it represents the new standard for regional anesthesia in terms of efficacy and safety. The ability to visualize nerve location, needle advancement, needle-nerve interaction, and local anesthetic spread makes ultrasound-guided nerve block an attractive option. Study results indicate that these advantages can improve the ease of block performance, block success rates, and complications. At the same time there is evidence that ultrasound-guided regional anesthesia is a unique skill in its own right, and that proficiency in it requires training and experience. Ultrasound is a valuable tool that is now available to the regional anesthesiologist, and it is fast becoming a standard part of practice. It promises to be of especial value to the less experienced practitioner. Ultrasound does not in itself, however, guarantee the efficacy and safety of peripheral nerve blockade. Proper training in its use is required and we can expect to see the development of formal standards and guidelines in this regard.
Ultrasound of the Brachial Plexus.
Griffith, James F
2018-07-01
Examination of the brachial plexus with ultrasound is efficient because it allows many parts of the brachial plexus as well as the surrounding soft tissues to be assessed with high spatial resolution. The key to performing good ultrasound of the brachial plexus is being familiar with the anatomy and the common variants. That makes it possible to concentrate solely on the ultrasound appearances free of simultaneously wondering about the anatomy. Ultrasound of the brachial plexus is particularly good for assessing nerve sheath tumor, perineural fibrosis, metastases, some inflammatory neuropathies, neuralgic amyotrophy, and posttraumatic sequalae. It is limited in the assessment of thoracic outlet syndrome and in the acute/subacute trauma setting. This review addresses the anatomy, ultrasound technique, as well as pathology of the brachial plexus from the cervical foramina to the axilla. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Ultrasound technology: A decision-making tool
USDA-ARS?s Scientific Manuscript database
An ultrasound demonstration was conducted for participants (~ 110 people) of the Arkansas Cattle Grower’s Conference, Hope, AR. Evaluation of live animals with ultrasound technology allows beef producers the ability to make selection and management decisions. Specifically, ultrasound at the conclu...
Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.
Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan
2017-07-01
Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
WE-A-210-00: Educational: Diagnostic Ultrasound QA
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
This presentation will focus on the present role of ultrasound medical physics in clinical practices. The first part of the presentation will provide an overview of ultrasound QC methodologies and testing procedures. A brief review of ultrasound phantoms utilized in these testing procedures will be presented. The second part of the presentation will summarize ultrasound imaging technical standards and professional guidelines by American College of Radiology (ACR), American Institute of Ultrasound in Medicine (AIUM), American Association of Physicists in Medicine (AAPM) and International Electrotechnical Commission (IEC). The current accreditation requirements by ACR and AIUM for ultrasound practices will be describedmore » and the practical aspects of implementing QC programs to be compliant with these requirements will be discussed. Learning Objectives: Achieve familiarity with common ultrasound QC test methods and ultrasound phantoms. Understand the coverage of the existing testing standards and professional guidelines on diagnostic ultrasound imaging. Learn what a medical physicist needs to know about ultrasound program accreditation and be able to implement ultrasound QC programs accordingly.« less
Novel design of low noise preamplifier for medical ultrasound transducers.
Amer, Mashhour Bani
2011-02-01
A novel design of low noise amplifier for medical ultrasound transducers is described in this paper. Unlike conventional low noise preamplifiers, this design proposes a new circuit configuration which has electronically adjustable matching resistance that allows the preamplifier to be compatible with a variety of medical ultrasound transducers. The design employs current feedback operational amplifier to enhance the gain-bandwidth independence and improve the design slew rate. Simulation results show that the proposed design has very low output noise voltage spectral density and the level of this noise does not increase when its tunable matching resistance is increased or decreased.
Lindfors, Hanna E; Drijfhout, Jan Wouter; Ubbink, Marcellus
2012-06-01
The interaction between the tyrosine kinases Src and focal adhesion kinase (FAK) is a key step in signaling processes from focal adhesions. The phosphorylated tyrosine residue 397 in FAK is able to bind the Src SH2 domain. To establish the extent of the FAK binding motif, the binding affinity of the SH2 domain for phosphorylated and unphosphorylated FAK-derived peptides of increasing length was determined and compared with that of the internal Src SH2 binding site. It is shown that the FAK peptides have higher affinity than the internal binding site and that seven negative residues adjacent to the core SH2 binding motif increase the binding constant 30-fold. A rigid spin-label incorporated in the FAK peptides was used to establish on the basis of paramagnetic relaxation enhancement whether the peptide-protein complex is well defined. A large spread of the paramagnetic effects on the surface of the SH2 domain suggests that the peptide-protein complex exhibits dynamics, despite the high affinity of the peptide. The strong electrostatic interaction between the positive side of the SH2 domain and the negative peptide results in a high affinity but may also favor a dynamic interaction. Copyright © 2012 Wiley Periodicals, Inc.
A review on lipase-catalyzed reactions in ultrasound-assisted systems.
Lerin, Lindomar A; Loss, Raquel A; Remonatto, Daniela; Zenevicz, Mara Cristina; Balen, Manuela; Netto, Vendelino Oenning; Ninow, Jorge L; Trentin, Cláudia M; Oliveira, J Vladimir; de Oliveira, Débora
2014-12-01
The named "green chemistry" has been receiving increasing prominence due to its environmentally friendly characteristics. The use of enzymes as catalysts in processes of synthesis to replace the traditional use of chemical catalysts present as main advantage the fact of following the principles of the green chemistry. However, processes of enzymatic nature generally provide lower yields when compared to the conventional chemical processes. Therefore, in the last years, the ultrasound has been extensively used in enzymatic processes, such as the production of esters with desirable characteristics for the pharmaceutical, cosmetics, and food industry, for the hydrolysis and glycerolysis of vegetable oils, production of biodiesel, etc. Several works found in the open literature suggest that the energy released by the ultrasound during the cavitation phenomena can be used to enhance mass transfer (substrate/enzyme), hence increasing the rate of products formation, and also contributing to enhance the enzyme catalytic activity. Furthermore, the ultrasound is considered a "green" technology due to its high efficiency, low instrumental requirement and significant reduction of the processing time in comparison to other techniques. The main goal of this review was to summarize studies available to date regarding the application of ultrasound in enzyme-catalyzed esterification, hydrolysis, glycerolysis and transesterification reactions.
Validation of Greyscale-Based Quantitative Ultrasound in Manual Wheelchair Users
Collinger, Jennifer L.; Fullerton, Bradley; Impink, Bradley G.; Koontz, Alicia M.; Boninger, Michael L.
2010-01-01
Objective The primary aim of this study is to establish the validity of greyscale-based quantitative ultrasound (QUS) measures of the biceps and supraspinatus tendons. Design Nine QUS measures of the biceps and supraspinatus tendons were computed from ultrasound images collected from sixty-seven manual wheelchair users. Shoulder pathology was measured using questionnaires, physical examination maneuvers, and a clinical ultrasound grading scale. Results Increased age, duration of wheelchair use, and body mass correlated with a darker, more homogenous tendon appearance. Subjects with pain during physical examination tests for biceps tenderness and acromioclavicular joint tenderness exhibited significantly different supraspinatus QUS values. Even when controlling for tendon depth, QUS measures of the biceps tendon differed significantly between subjects with healthy tendons, mild tendinosis, and severe tendinosis. Clinical grading of supraspinatus tendon health was correlated with QUS measures of the supraspinatus tendon. Conclusions Quantitative ultrasound is valid method to quantify tendinopathy and may allow for early detection of tendinosis. Manual wheelchair users are at a high risk for developing shoulder tendon pathology and may benefit from quantitative ultrasound-based research that focuses on identifying interventions designed to reduce this risk. PMID:20407304
Shaifta, Yasin; Irechukwu, Nneka; Prieto‐Lloret, Jesus; MacKay, Charles E; Marchon, Keisha A; Ward, Jeremy P T
2015-01-01
Background and Purpose The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src‐family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR‐mediated ASM contraction and associated signalling events. Experimental Approach Contraction was recorded in intact or α‐toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light‐chain‐20 (MLC20) and myosin phosphatase targeting subunit‐1 (MYPT‐1) was evaluated in cultured human ASM cells (hASMC). [Ca2+]i was evaluated in Fura‐2 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined. Key Results Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho‐kinase, while after α‐toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho‐kinase, but not FAK. CCh and BK increased phosphorylation of MYPT‐1 and MLC20 and auto‐phosphorylation of SrcFK and FAK. MYPT‐1 phosphorylation was sensitive to inhibition of Rho‐kinase and SrcFK, but not FAK. Contraction induced by SR Ca2+ depletion and equivalent [Ca2+]i responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization‐induced contraction was sensitive to FAK inhibition only. SrcFK auto‐phosphorylation was partially FAK‐dependent, while FAK auto‐phosphorylation was SrcFK‐independent. Conclusions and Implications SrcFK mediates Ca2+‐sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca2+ influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease. PMID:26294392
Daoudi, K; van den Berg, P J; Rabot, O; Kohl, A; Tisserand, S; Brands, P; Steenbergen, W
2014-10-20
Ultrasound and photoacoustics can be utilized as complementary imaging techniques to improve clinical diagnoses. Photoacoustics provides optical contrast and functional information while ultrasound provides structural and anatomical information. As of yet, photoacoustic imaging uses large and expensive systems, which limits their clinical application and makes the combination costly and impracticable. In this work we present and evaluate a compact and ergonomically designed handheld probe, connected to a portable ultrasound system for inexpensive, real-time dual-modality ultrasound/photoacoustic imaging. The probe integrates an ultrasound transducer array and a highly efficient diode stack laser emitting 130 ns pulses at 805 nm wavelength and a pulse energy of 0.56 mJ, with a high pulse repetition frequency of up to 10 kHz. The diodes are driven by a customized laser driver, which can be triggered externally with a high temporal stability necessary to synchronize the ultrasound detection and laser pulsing. The emitted beam is collimated with cylindrical micro-lenses and shaped using a diffractive optical element, delivering a homogenized rectangular light intensity distribution. The system performance was tested in vitro and in vivo by imaging a human finger joint.
Palumbo, P; Cinque, B; Miconi, G; La Torre, C; Zoccali, G; Vrentzos, N; Vitale, A R; Leocata, P; Lombardi, D; Lorenzo, C; D'Angelo, B; Macchiarelli, G; Cimini, A; Cifone, M G; Giuliani, M
2011-01-01
the spatial architecture. The analysis of the composition of lipids in the fat released from adipose tissue after ultrasound treatment with surgical device showed, in agreement with the level of adipocyte damage, a significant increase mainly of triglycerides and cholesterol. Finally, ultrasound exposure had been shown to induce apoptosis as shown by the appearance DNA fragmentation. Accordingly, ultrasound treatment led to down-modulation of procaspase-9 expression and an increased level of caspase-3 active form.
Droplets, Bubbles and Ultrasound Interactions.
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.
Ultrasound: Abdomen (For Parents)
... the computer screen. A technician (sonographer) trained in ultrasound imaging will spread a clear, warm gel on the skin of the abdomen. This gel helps with the transmission of the sound waves. The ... abdominal ultrasound is painless. Your child may feel a slight ...
Ultrasound: Head (For Parents)
... the computer screen. A technician (sonographer) trained in ultrasound imaging will spread a clear, warm gel on your child's scalp (over the fontanel). This gel helps with the transmission of the ... Expect The head ultrasound test is painless, though your child may feel ...
Ultrasound strain imaging using Barker code
NASA Astrophysics Data System (ADS)
Peng, Hui; Tie, Juhong; Guo, Dequan
2017-01-01
Ultrasound strain imaging is showing promise as a new way of imaging soft tissue elasticity in order to help clinicians detect lesions or cancers in tissues. In this paper, Barker code is applied to strain imaging to improve its quality. Barker code as a coded excitation signal can be used to improve the echo signal-to-noise ratio (eSNR) in ultrasound imaging system. For the Baker code of length 13, the sidelobe level of the matched filter output is -22dB, which is unacceptable for ultrasound strain imaging, because high sidelobe level will cause high decorrelation noise. Instead of using the conventional matched filter, we use the Wiener filter to decode the Barker-coded echo signal to suppress the range sidelobes. We also compare the performance of Barker code and the conventional short pulse in simulation method. The simulation results demonstrate that the performance of the Wiener filter is much better than the matched filter, and Baker code achieves higher elastographic signal-to-noise ratio (SNRe) than the short pulse in low eSNR or great depth conditions due to the increased eSNR with it.
The Sound Games: Introducing Gamification into Stanford's Orientation on Emergency Ultrasound.
Lobo, Viveta; Stromberg, Andrew Q; Rosston, Peter
2017-09-18
Point-of-care ultrasound is a critical component of graduate medical training in emergency medicine. Innovation in ultrasound teaching methods is greatly needed to keep up with a changing medical landscape. A field-wide trend promoting simulation and technology-enhanced learning is underway in an effort to improve patient care, as well as patient safety. In an effort to both motivate students and increase their skill retention, training methods are shifting towards a friendly competition model and are gaining popularity nationwide. In line with this emerging trend, Stanford incorporated the Sound Games - an educational ultrasound event with a distinctly competitive thread - within its existing two-day point-of-care ultrasound orientation course for emergency medicine interns. In this study, we demonstrate successful implementation of the orientation program, significant learning gains in participants, and overall student satisfaction with the course.
Internal Medicine Residents' Retention of Knowledge and Skills in Bedside Ultrasound.
Town, James A; Bergl, Paul A; Narang, Akhil; McConville, John F
2016-10-01
The long-term retention of knowledge and skills in bedside ultrasound by internal medicine residents after ultrasound training is not well understood. We sought to determine whether knowledge and skills acquired from focused training in bedside ultrasound are retained over time, and whether retention is related to independent practice. We conducted a prospective observational trial of 101 internal medicine residents at an academic medical center who participated in a bedside ultrasound workshop followed by 12 months of independent practice. Performance was measured on image-based knowledge and skills assessment using direct observation, both before the workshop and 12 months later. Individual usage data were obtained along with a survey on attitudes toward bedside ultrasound. Participants' mean knowledge assessment score increased from a baseline of 63.7% to 84.5% immediately after training ( P < .001). At 12 months, mean knowledge score fell to 73.0%, significantly different from both prior assessments ( P < .001). Despite knowledge decline, the mean skills assessment score improved from a baseline of 30.5% to 50.4% at 12 months ( P < .001). Residents reporting more ultrasound use (> 25 examinations) had higher scores in baseline knowledge and skills assessments than those with lower usage (< 25 examinations). Change in knowledge and image acquisition skills between assessments was equal in both subgroups. Residents' knowledge of ultrasound improved after brief training but decayed over time, whereas skills showed marginal improvement over the study, with minimal support. Growth and retention of ultrasound abilities were not impacted by usage rates.
Internal Medicine Residents' Retention of Knowledge and Skills in Bedside Ultrasound
Town, James A.; Bergl, Paul A.; Narang, Akhil; McConville, John F.
2016-01-01
ABSTRACT Background The long-term retention of knowledge and skills in bedside ultrasound by internal medicine residents after ultrasound training is not well understood. Objective We sought to determine whether knowledge and skills acquired from focused training in bedside ultrasound are retained over time, and whether retention is related to independent practice. Methods We conducted a prospective observational trial of 101 internal medicine residents at an academic medical center who participated in a bedside ultrasound workshop followed by 12 months of independent practice. Performance was measured on image-based knowledge and skills assessment using direct observation, both before the workshop and 12 months later. Individual usage data were obtained along with a survey on attitudes toward bedside ultrasound. Results Participants' mean knowledge assessment score increased from a baseline of 63.7% to 84.5% immediately after training (P < .001). At 12 months, mean knowledge score fell to 73.0%, significantly different from both prior assessments (P < .001). Despite knowledge decline, the mean skills assessment score improved from a baseline of 30.5% to 50.4% at 12 months (P < .001). Residents reporting more ultrasound use (> 25 examinations) had higher scores in baseline knowledge and skills assessments than those with lower usage (< 25 examinations). Change in knowledge and image acquisition skills between assessments was equal in both subgroups. Conclusions Residents' knowledge of ultrasound improved after brief training but decayed over time, whereas skills showed marginal improvement over the study, with minimal support. Growth and retention of ultrasound abilities were not impacted by usage rates. PMID:27777666
Stable phantom materials for ultrasound and optical imaging.
Cabrelli, Luciana C; Pelissari, Pedro I B G B; Deana, Alessandro M; Carneiro, Antonio A O; Pavan, Theo Z
2017-01-21
Phantoms mimicking the specific properties of biological tissues are essential to fully characterize medical devices. Water-based materials are commonly used to manufacture phantoms for ultrasound and optical imaging techniques. However, these materials have disadvantages, such as easy degradation and low temporal stability. In this study, we propose an oil-based new tissue-mimicking material for ultrasound and optical imaging, with the advantage of presenting low temporal degradation. A styrene-ethylene/butylene-styrene (SEBS) copolymer in mineral oil samples was made varying the SEBS concentration between 5%-15%, and low-density polyethylene (LDPE) between 0%-9%. Acoustic properties, such as the speed of sound and the attenuation coefficient, were obtained using frequencies ranging from 1-10 MHz, and were consistent with that of soft tissues. These properties were controlled varying SEBS and LDPE concentration. To characterize the optical properties of the samples, the diffuse reflectance and transmittance were measured. Scattering and absorption coefficients ranging from 400 nm-1200 nm were calculated for each compound. SEBS gels are a translucent material presenting low optical absorption and scattering coefficients in the visible region of the spectrum, but the presence of LDPE increased the turbidity. Adding LDPE increased the absorption and scattering of the phantom materials. Ultrasound and photoacoustic images of a heterogeneous phantom made of LDPE/SEBS containing a spherical inclusion were obtained. Annatto dye was added to the inclusion to enhance the optical absorbance. The results suggest that copolymer gels are promising for ultrasound and optical imaging, making them also potentially useful for photoacoustic imaging.
Stable phantom materials for ultrasound and optical imaging
NASA Astrophysics Data System (ADS)
Cabrelli, Luciana C.; Pelissari, Pedro I. B. G. B.; Deana, Alessandro M.; Carneiro, Antonio A. O.; Pavan, Theo Z.
2017-01-01
Phantoms mimicking the specific properties of biological tissues are essential to fully characterize medical devices. Water-based materials are commonly used to manufacture phantoms for ultrasound and optical imaging techniques. However, these materials have disadvantages, such as easy degradation and low temporal stability. In this study, we propose an oil-based new tissue-mimicking material for ultrasound and optical imaging, with the advantage of presenting low temporal degradation. A styrene-ethylene/butylene-styrene (SEBS) copolymer in mineral oil samples was made varying the SEBS concentration between 5%-15%, and low-density polyethylene (LDPE) between 0%-9%. Acoustic properties, such as the speed of sound and the attenuation coefficient, were obtained using frequencies ranging from 1-10 MHz, and were consistent with that of soft tissues. These properties were controlled varying SEBS and LDPE concentration. To characterize the optical properties of the samples, the diffuse reflectance and transmittance were measured. Scattering and absorption coefficients ranging from 400 nm-1200 nm were calculated for each compound. SEBS gels are a translucent material presenting low optical absorption and scattering coefficients in the visible region of the spectrum, but the presence of LDPE increased the turbidity. Adding LDPE increased the absorption and scattering of the phantom materials. Ultrasound and photoacoustic images of a heterogeneous phantom made of LDPE/SEBS containing a spherical inclusion were obtained. Annatto dye was added to the inclusion to enhance the optical absorbance. The results suggest that copolymer gels are promising for ultrasound and optical imaging, making them also potentially useful for photoacoustic imaging.
Nonlinear absorption in biological tissue for high intensity focused ultrasound.
Liu, Xiaozhou; Li, Junlun; Gong, Xiufen; Zhang, Dong
2006-12-22
In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.
Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound
NASA Astrophysics Data System (ADS)
Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph
2013-11-01
Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity.
Evaluating Rebar Corrosion Using Nonlinear Ultrasound
NASA Astrophysics Data System (ADS)
Woodward, Clinton; Amin, Md. Nurul
2008-02-01
The early detection of rebar corrosion in reinforced concrete is difficult using current methods. This pilot study investigated the viability of using nonlinear ultrasound to detect the effects of rebar corrosion in its early stages. The study utilized three accelerated corrosion specimens and one control specimen. Results showed that when corrosion developed in the area isonified by a Rayleigh wave, nonlinear parameters increased. As corrosion progressed, these nonlinear parameters also increased.
Focused ultrasound and microbubbles for enhanced extravasation.
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.
Ultrasound Images of the Tongue: A Tutorial for Assessment and Remediation of Speech Sound Errors.
Preston, Jonathan L; McAllister Byun, Tara; Boyce, Suzanne E; Hamilton, Sarah; Tiede, Mark; Phillips, Emily; Rivera-Campos, Ahmed; Whalen, Douglas H
2017-01-03
Diagnostic ultrasound imaging has been a common tool in medical practice for several decades. It provides a safe and effective method for imaging structures internal to the body. There has been a recent increase in the use of ultrasound technology to visualize the shape and movements of the tongue during speech, both in typical speakers and in clinical populations. Ultrasound imaging of speech has greatly expanded our understanding of how sounds articulated with the tongue (lingual sounds) are produced. Such information can be particularly valuable for speech-language pathologists. Among other advantages, ultrasound images can be used during speech therapy to provide (1) illustrative models of typical (i.e. "correct") tongue configurations for speech sounds, and (2) a source of insight into the articulatory nature of deviant productions. The images can also be used as an additional source of feedback for clinical populations learning to distinguish their better productions from their incorrect productions, en route to establishing more effective articulatory habits. Ultrasound feedback is increasingly used by scientists and clinicians as both the expertise of the users increases and as the expense of the equipment declines. In this tutorial, procedures are presented for collecting ultrasound images of the tongue in a clinical context. We illustrate these procedures in an extended example featuring one common error sound, American English /r/. Images of correct and distorted /r/ are used to demonstrate (1) how to interpret ultrasound images, (2) how to assess tongue shape during production of speech sounds, (3), how to categorize tongue shape errors, and (4), how to provide visual feedback to elicit a more appropriate and functional tongue shape. We present a sample protocol for using real-time ultrasound images of the tongue for visual feedback to remediate speech sound errors. Additionally, example data are shown to illustrate outcomes with the procedure.
Hsieh, Yih-Shou; Chu, Shu-Chen; Hsu, Li-Sung; Chen, Kuo-Shuen; Lai, Ming-Tsung; Yeh, Chia-Heng; Chen, Pei-Ni
2013-12-01
Epithelial to mesenchymal transition (EMT) has been considered essential for cancer metastasis, a multistep complicated process including local invasion, intravasation, extravasation, and proliferation at distant sites. Herein we provided molecular evidence associated with the antimetastatic effect of Rubus idaeus L. extracts (RIE) by showing a nearly complete inhibition on the invasion (p<0.001) of highly metastatic A549 cells via reduced activities of matrix metalloproteinase-2 (MMP-2) and urokinasetype plasminogen activator (u-PA). We performed Western blot to find that RIE could induce up-regulation of epithelial marker such as E-cadherin and α-catenin and inhibit the mesenchymal markers such as N-cadherin, fibronectin, snail-1, and vimentin. Selective snail-1 inhibition by snail-1-specific-siRNA also showed increased E-cadherin expression in A549 cells suggesting a possible involvement of snail-1 inhibition in RIE-caused increase in E-cadherin level. RIE also inhibited p-FAK, p-paxillin and AP-1 by Western blot analysis, indicating the anti-EMT effect of RIE in human lung carcinoma. Importantly, an in vivo BALB/c nude mice xenograft model showed that RIE treatment reduced tumor growth by oral gavage, and RIE represent promising candidates for future phytochemical-based mechanistic pathway-targeted cancer prevention strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.
Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo study
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
Lenzi, Paola; Gambardella, Stefano; Ferese, Rosangela; Calierno, Maria Teresa; Falleni, Alessandra; Grimaldi, Alfonso; Frati, Alessandro; Esposito, Vincenzo; Limatola, Cristina; Fornai, Francesco
2017-01-01
Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin. In these experimental conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing long branches. Rapamycin suppressed cell migration when exposed to fetal bovine serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The present study improves our awareness of basic mechanisms which relate mTOR activity to the biology of glioblastoma cells. These findings apply to a variety of effects which can be induced by mTOR regulation in the brain. In fact, the ability to promote neuronal differentiation might be viewed as a novel therapeutic pathway to approach neuronal regeneration. PMID:28418837
Ferrucci, Michela; Biagioni, Francesca; Lenzi, Paola; Gambardella, Stefano; Ferese, Rosangela; Calierno, Maria Teresa; Falleni, Alessandra; Grimaldi, Alfonso; Frati, Alessandro; Esposito, Vincenzo; Limatola, Cristina; Fornai, Francesco
2017-05-02
Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin. In these experimental conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing long branches. Rapamycin suppressed cell migration when exposed to fetal bovine serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The present study improves our awareness of basic mechanisms which relate mTOR activity to the biology of glioblastoma cells. These findings apply to a variety of effects which can be induced by mTOR regulation in the brain. In fact, the ability to promote neuronal differentiation might be viewed as a novel therapeutic pathway to approach neuronal regeneration.
Registration of surface structures using airborne focused ultrasound.
Sundström, N; Börjesson, P O; Holmer, N G; Olsson, L; Persson, H W
1991-01-01
A low-cost measuring system, based on a personal computer combined with standard equipment for complex measurements and signal processing, has been assembled. Such a system increases the possibilities for small hospitals and clinics to finance advanced measuring equipment. A description of equipment developed for airborne ultrasound together with a personal computer-based system for fast data acquisition and processing is given. Two air-adapted ultrasound transducers with high lateral resolution have been developed. Furthermore, a few results for fast and accurate estimation of signal arrival time are presented. The theoretical estimation models developed are applied to skin surface profile registrations.
Ultrasound Fracture Diagnosis in Space
NASA Technical Reports Server (NTRS)
Dulchavsky, Scott A.; Amponsah, David; Sargsyan, Ashot E.; Garcia, Kathleen M.; Hamilton, Douglas R.; vanHolsbeeck, Marnix
2010-01-01
Introduction: This ground-based investigation accumulated high-level clinical evidence on the sensitivity and specificity of point of care ultrasound performed by expert and novice users for the rapid diagnosis of musculoskeletal (MSK) injuries. We developed preliminary educational methodologies to provide just-in-time training of novice users by creating multi-media training tools and imaging procedures for non expert operators and evaluated the sensitivity and specificity of non-expert performed musculoskeletal ultrasound to diagnose acute injuries in a Level 1 Trauma Center. Methods: Patients with potential MSK injuries were identified in the emergency room. A focused MSK ultrasound was performed by expert operators and compared to standard radiographs. A repeat examination was performed by non-expert operators who received a short, just-in-time multimedia education aid. The sensitivity and specificity of the expert and novice ultrasound examinations were compared to gold standard radiography. Results: Over 800 patients were enrolled in this study. The sensitivity and specificity of expert performed ultrasound exceeded 98% for MSK injuries. Novice operators achieved 97% sensitivity and 99% specificity for targeted examinations with the greatest error in fractures involving the hand and foot. Conclusion: Point of care ultrasound is a sensitive and specific diagnostic test for MSK injury when performed by experts and just-in-time trained novice operators.
Riemenschneider, Markus J; Mueller, Wolf; Betensky, Rebecca A; Mohapatra, Gayatry; Louis, David N
2005-11-01
Deregulated integrin signaling is common in cancers, including glioblastoma. Integrin binding and growth factor receptor signaling activate focal adhesion kinase (FAK) and subsequently up-regulate extracellular regulated kinases (ERK-1/2), leading to cell-cycle progression and cell migration. Most studies of this pathway have used in vitro systems or tumor lysate-based approaches. We examined these pathways primarily in situ using a panel of 30 glioblastomas and gene expression arrays, immunohistochemistry, and fluorescence in situ hybridization, emphasizing the histological distribution of molecular changes. Within individual tumors, increased expression of FAK, p-FAK, paxillin, ERK-1/2, and p-ERK-1/2 occurred in regions of elevated EGFR and/or PDGFRA expression. Moreover, FAK activation levels correlated with EGFR and PDGFRA expression, and p-FAK and EGFR expression co-localized at the single-cell level. In addition, integrin expression was enriched in EGFR/PDGFRA-overexpressing areas but was more regionally confined than FAK, p-FAK, and paxillin. Integrins beta8 and alpha5beta1 were most commonly expressed, often in a perinecrotic or perivascular pattern. Taken together, our data suggest that growth factor receptor overexpression facilitates alterations in the integrin signaling pathway. Thus, FAK may act in glioblastoma as a downstream target of growth factor signaling, with integrins enhancing the impact of such signaling in the tumor microenvironment.
Kim, Mi Sung; Kwon, Heon-Ju; Kang, Kyung A; Do, In-Gu; Park, Hee-Jin; Kim, Eun Young; Hong, Hyun Pyo; Choi, Yoon Jung; Kim, Young Hwan
2018-02-01
To evaluate the diagnostic performance of ultrasound and to determine which ultrasound findings are useful to differentiate appendicitis from non-appendicitis in patients who underwent ultrasound re-evaluation owing to equivocal CT features of acute appendicitis. 62 patients who underwent CT examinations for suspected appendicitis followed by ultrasound re-evaluation owing to equivocal CT findings were included. Equivocal CT findings were considered based on the presence of only one or two findings among the CT criteria, and ultrasound re-evaluation was done based on a predefined structured report form. The diagnostic performance of ultrasound and independent variables to discriminate appendicitis from non-appendicitis were assessed. There were 27 patients in the appendicitis group. The overall diagnostic performance of ultrasound re-evaluation was sensitivity of 96.3%, specificity of 91.2% and accuracy of 91.9%. In terms of the performance of individual ultrasound findings, probe-induced tenderness showed the highest accuracy (86.7%) with sensitivity of 74% and specificity of 97%, followed by non-compressibility (accuracy 71.7%, sensitivity 85.2% and specificity 60.6%). The independent ultrasound findings for discriminating appendicitis were non-compressibility (p = 0.002) and increased flow on the appendiceal wall (p = 0.001). Ultrasound re-evaluation can be used to improve diagnostic accuracy in cases with equivocal CT features for diagnosing appendicitis. The presence of non-compressibility and increased vascular flow on the appendix wall are useful ultrasound findings to discriminate appendicitis from non-appendicitis. Advances in knowledge: Ultrasound re-evaluation is useful to discriminate appendicitis from non-appendicitis when CT features are inconclusive.
Functional assessment of the diaphragm by speckle tracking ultrasound during inspiratory loading.
Oppersma, Eline; Hatam, Nima; Doorduin, Jonne; van der Hoeven, Johannes G; Marx, Gernot; Goetzenich, Andreas; Fritsch, Sebastian; Heunks, Leo M A; Bruells, Christian S
2017-11-01
Assessment of diaphragmatic effort is challenging, especially in critically ill patients in the phase of weaning. Fractional thickening during inspiration assessed by ultrasound has been used to estimate diaphragm effort. It is unknown whether more sophisticated ultrasound techniques such as speckle tracking are superior in the quantification of inspiratory effort. This study evaluates the validity of speckle tracking ultrasound to quantify diaphragm contractility. Thirteen healthy volunteers underwent a randomized stepwise threshold loading protocol of 0-50% of the maximal inspiratory pressure. Electric activity of the diaphragm and transdiaphragmatic pressures were recorded. Speckle tracking ultrasound was used to assess strain and strain rate as measures of diaphragm tissue deformation and deformation velocity, respectively. Fractional thickening was assessed by measurement of diaphragm thickness at end-inspiration and end-expiration. Strain and strain rate increased with progressive loading of the diaphragm. Both strain and strain rate were highly correlated to transdiaphragmatic pressure (strain r 2 = 0.72; strain rate r 2 = 0.80) and diaphragm electric activity (strain r 2 = 0.60; strain rate r 2 = 0.66). We conclude that speckle tracking ultrasound is superior to conventional ultrasound techniques to estimate diaphragm contractility under inspiratory threshold loading. NEW & NOTEWORTHY Transdiaphragmatic pressure using esophageal and gastric balloons is the gold standard to assess diaphragm effort. However, this technique is invasive and requires expertise, and the interpretation may be complex. We report that speckle tracking ultrasound can be used to detect stepwise increases in diaphragmatic effort. Strain and strain rate were highly correlated with transdiaphragmatic pressure, and therefore, diaphragm electric activity and speckle tracking might serve as reliable tools to quantify diaphragm effort in the future. Copyright © 2017 the
Ultrasound of skeletal muscle injury.
Koh, Eamon Su Chun; McNally, Eugene G
2007-06-01
The professional and recreational demands of modern society make the treatment of muscle injury an increasingly important clinical problem, particularly in the athletic population. In the elite athlete, significant financial and professional pressures may also exist that emphasize the need for accurate diagnosis and treatment. With new advances in ultrasound technology, images of exquisite detail allow diagnosis of muscle injury that matches the accuracy of magnetic resonance imaging (MRI). Furthermore, the benefits of real-time and Doppler imaging, ability to perform interventional procedures, and relative cost benefits compared with MRI place ultrasound at the forefront for investigation for these injuries in many circumstances. Muscle injury may be divided into acute and chronic pathology, with muscle strain injury the most common clinical problem presenting to sports physicians. This article reviews the spectrum of acute and chronic muscle injuries, with particular attention to clinical features and some common or important muscle strain injuries.
Li, Dan-Dan; Xu, Hui-Xiong; Guo, Le-Hang; Bo, Xiao-Wan; Li, Xiao-Long; Wu, Rong; Xu, Jun-Mei; Zhang, Yi-Feng; Zhang, Kun
2016-09-01
To evaluate the diagnostic performance of a new method of combined two-dimensional shear wave elastography (i.e. virtual touch imaging quantification, VTIQ) and ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) in the differential diagnosis of breast lesions. From September 2014 to December 2014, 276 patients with 296 pathologically proven breast lesions were enrolled in this study. The conventional US images were interpreted by two independent readers. The diagnosis performances of BI-RADS and combined BI-RADS and VTIQ were evaluated, including the area under the receiver operating characteristic curve (AUROC), sensitivity and specificity. Observer consistency was also evaluated. Pathologically, 212 breast lesions were benign and 84 were malignant. Compared with BI-RADS alone, the AUROCs and specificities of the combined method for both readers increased significantly (AUROC: 0.862 vs. 0.693 in reader 1, 0.861 vs. 0.730 in reader 2; specificity: 91.5 % vs. 38.7 % in reader 1, 94.8 % vs. 47.2 % in reader 2; all P < .05). The Kappa value between the two readers for BI-RADS assessment was 0.614, and 0.796 for the combined method. The combined VTIQ and BI-RADS had a better diagnostic performance in the diagnosis of breast lesions in comparison with BI-RADS alone. • Combination of conventional ultrasound and elastography distinguishes breast cancers more effectively. • Combination of conventional ultrasound and elastography increases observer consistency. • BI-RADS weights more than the 2D-SWE with an increase in malignancy probability.
Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Shi, Dennis; Kumar, Kaushlendra; Goodwin, Andrew P
2017-09-01
The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL -1 (7 × 10 9 particles mL -1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Trained simulated ultrasound patients: medical students as models, learners, and teachers.
Blickendorf, J Matthew; Adkins, Eric J; Boulger, Creagh; Bahner, David P
2014-01-01
Medical educators must develop ultrasound education programs to ensure that future physicians are prepared to face the changing demands of clinical practice. It can be challenging to find human models for hands-on scanning sessions. This article outlines an educational model from a large university medical center that uses medical students to fulfill the need for human models. During the 2011-2012 academic year, medical students from The Ohio State University College of Medicine served as trained simulated ultrasound patients (TSUP) for hands-on scanning sessions held by the college and many residency programs. The extracurricular program is voluntary and coordinated by medical students with faculty supervision. Students receive a longitudinal didactic and hands-on ultrasound education program as an incentive for serving as a TSUP. The College of Medicine and 7 residency programs used the program, which included 47 second-year and 7 first-year student volunteers. Participation has increased annually because of the program's ease, reliability, and cost savings in providing normal anatomic models for ultrasound education programs. A key success of this program is its inherent reproducibility, as a new class of eager students constitutes the volunteer pool each year. The TSUP program is a feasible and sustainable method of fulfilling the need for normal anatomic ultrasound models while serving as a valuable extracurricular ultrasound education program for medical students. The program facilitates the coordination of ultrasound education programs by educators at the undergraduate and graduate levels.
2017-01-01
A number of queries regarding the paper ‘Are some people suffering as a result of increasing mass exposure of the public to ultrasound in air?’ (Leighton 2016 Proc. R. Soc. A 472, 20150624 (doi:10.1098/rspa.2015.0624)) have been sent in from readers, almost all based around some or all of a small set of questions. These can be grouped into issues of engineering, human factors and timeliness. Those issues (represented by the most typical wording used in queries) and my responses are summarized in this comment. PMID:28413349
Ultrasound visual feedback treatment and practice variability for residual speech sound errors
Preston, Jonathan L.; McCabe, Patricia; Rivera-Campos, Ahmed; Whittle, Jessica L.; Landry, Erik; Maas, Edwin
2014-01-01
Purpose The goals were to (1) test the efficacy of a motor-learning based treatment that includes ultrasound visual feedback for individuals with residual speech sound errors, and (2) explore whether the addition of prosodic cueing facilitates speech sound learning. Method A multiple baseline single subject design was used, replicated across 8 participants. For each participant, one sound context was treated with ultrasound plus prosodic cueing for 7 sessions, and another sound context was treated with ultrasound but without prosodic cueing for 7 sessions. Sessions included ultrasound visual feedback as well as non-ultrasound treatment. Word-level probes assessing untreated words were used to evaluate retention and generalization. Results For most participants, increases in accuracy of target sound contexts at the word level were observed with the treatment program regardless of whether prosodic cueing was included. Generalization between onset singletons and clusters was observed, as well as generalization to sentence-level accuracy. There was evidence of retention during post-treatment probes, including at a two-month follow-up. Conclusions A motor-based treatment program that includes ultrasound visual feedback can facilitate learning of speech sounds in individuals with residual speech sound errors. PMID:25087938
Relea, A; Alonso, J A; González, M; Zornoza, C; Bahamonde, S; Viñuela, B E; Encinas, M B
2018-06-12
To determine whether the twinkling artifact on Doppler ultrasound imaging corresponds to microcalcifications previously seen on mammograms and to evaluate the usefulness of this finding in the ultrasound management of suspicious microcalcifications. We used ultrasonography to prospectively examine 46 consecutive patients with groups of microcalcifications suspicious for malignancy identified at mammography, searching for the presence of the twinkling artifact to identify the microcalcifications. Once we identified the microcalcifications, we obtained core-needle biopsy specimens with 11G needles and then used X-rays to check the specimens for the presence of microcalcifications. We analyzed the percentage of detection and obtainment of microcalcifications by core-needle biopsy with this technique and the radiopathologic correlation. Microcalcifications that were not detected by ultrasound or discordant lesions were biopsied by stereotaxy at another center. We also used ultrasound guidance for preoperative marking with clips, usually orienting them radially. We identified and biopsied 41 of the 46 lesions under ultrasound guidance, including 24 of 25 carcinomas (17 in situ). B-mode ultrasound was sufficient for biopsying the microcalcifications in 14 patients, although the presence of the twinkling artifact increased the number of microcalcifications detected and thus enabled more accurate preoperative marking. Thanks to the twinkling sign, we were able to identify 27 additional groups of microcalcifications (89% vs. 30%; p < 0.05). All the surgical specimens had margins free of disease. The twinkling artifact is useful for microcalcifications in ultrasound examinations, enabling a significant increase in the yield of ultrasound-guided biopsies and better preoperative marking of groups of microcalcifications. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Applicator for in-vitro ultrasound-activated targeted drug delivery
NASA Astrophysics Data System (ADS)
Gerold, B.; Gourevich, D.; Volovick, A.; Xu, D.; Arditti, F.; Prentice, P.; Cochran, S.; Gnaim, J.; Medan, Y.; Wang, L.; Melzer, A.
2012-10-01
Reducing toxicity and improving uptake of cancer drugs in tumors are important goals of targeted drug delivery (TDD). Ultrasonic drug release from various encapsulants has been a focus of many research groups. However, a single standard ultrasonic device, viable for use by biologists, is not currently present in the market. The device reported here is designed to allow investigation of the impact of ultrasound on cellular uptake and cell viability in-vitro. In it, single-element transducers with different operating frequencies are mounted below a standard 96-well plate. The plate is moved above the transducers, such that each line of wells can be sonicated at a different frequency. To assess the device, 96-well plates were seeded with cells and sonicated using different ultrasonic parameters, with and without doxorubicin. Cell viability was measured by colorimetric MTT assay and the uptake of doxorubicin by cells was also determined. The device proved to be highly viable in preliminary tests; it demonstrated that change in ultrasonic parameters produces different effect on cells. For example, increase in uptake of doxorubicin was demonstrated following ultrasound application. The growing interest in ultrasound-activated TDD emphasizes the need for standardization of the ultrasound device and the one reported here may offer some indications of how that may be achieved. It is planned to further improve the prototype by increasing the number of ultrasonic frequencies and degrees of freedom for each transducer.
Thyroid Nodule Size at Ultrasound as a Predictor of Malignancy and Final Pathologic Size.
Cavallo, Allison; Johnson, Daniel N; White, Michael G; Siddiqui, Saaduddin; Antic, Tatjana; Mathew, Melvy; Grogan, Raymon H; Angelos, Peter; Kaplan, Edwin L; Cipriani, Nicole A
2017-05-01
Thyroid-related mortality has remained constant despite the increasing incidence of thyroid carcinoma. Most thyroid nodules are benign; therefore, ultrasound and fine needle aspiration (FNA) are integral in cancer screening. We hypothesize that increased nodule size at ultrasound does not predict malignancy and correlation between nodule size at ultrasound and pathologic exam is good. Resected thyroids with preoperative ultrasounds were identified. Nodule size at ultrasound, FNA diagnosis by Bethesda category, size at pathologic examination, and final histologic diagnosis were recorded. Nodule characteristics at ultrasound and FNA diagnoses were correlated with gross characteristics and histologic diagnoses. Nodules for which correlation could not be established were excluded. Of 1003 nodules from 659 patients, 26% were malignant. Nodules <2 cm had the highest malignancy rate (∼30%). Risk was similar (∼20%) for nodules ≥2 cm. Of the 548 subject to FNA, 38% were malignant. Decreasing malignancy rates were observed with increasing size (57% for nodules <1 cm to 20% for nodules >6 cm). At ultrasound size cutoffs of 2, 3, 4, and 5 cm, smaller nodules had higher malignancy rates than larger nodules. Of the 455 not subject to FNA, 11% were malignant. Ultrasound size alone is a poor predictor of malignancy, but a relatively good predictor of final pathologic size (R 2 = 0.748), with less correlation at larger sizes. In nodules subject to FNA, false negative diagnoses were highest (6-8%) in nodules 3-6 cm, mostly due to encapsulated follicular variant of papillary carcinoma. Thyroid nodule size is inversely related to malignancy risk, as larger nodules have lower malignancy rates. However, the relationship of size to malignancy varies by FNA status. All nodules (regardless of FNA status) demonstrate a risk trough at ≥2 cm. Nodules subject to FNA show step-wise decline in malignancy rates by size, demonstrating that size alone should not be
Adiposis dolorosa (Dercum's disease): MRI and ultrasound appearances.
Tins, B J; Matthews, C; Haddaway, M; Cassar-Pullicino, V N; Lalam, R; Singh, J; Tyrrell, P N M
2013-10-01
To describe ultrasound and magnetic resonance imaging (MRI) features of adiposis dolorosa, Dercum's disease, and to evaluate the MRI features prospectively against a large number of MRI examinations. Institutional review board approval for this study was obtained. The imaging features at MRI and ultrasound of 13 cases of adiposis dolorosa (nine female, four male; age range 32-72 years) were reviewed. MRI findings typical for adiposis dolorosa were proposed and prospectively evaluated on 6247 MRI examinations performed over a period of 8 months. Adiposis dolorosa demonstrates multiple, oblong, fatty lesions in the superficial subcutaneous fatty tissue. They are mostly <2 cm in long axis diameter. They demonstrate nodular ("blush-like") increased fluid signal at unenhanced MRI and are markedly hyperechoic at ultrasound. There is no contrast medium enhancement at MRI and no increased Doppler signal at ultrasound. Most lesions were clinically asymptomatic, some were painful/tender. There was no imaging evidence of oedema or inflammation. During prospective validation of these MRI features on 6247 MRI examinations, two cases with typical imaging features were encountered; both were diagnosed as adiposis dolorosa on clinical review. All cases of adiposis dolorosa showed these imaging findings. This results in a very low likelihood that a nodular, blush-like appearance of subcutaneous fat on MRI is not due to adiposis dolorosa. Adiposis dolorosa, Dercum's disease, should be suggested in the presence of multiple (many) small, oblong, fatty lesions in the subcutaneous fatty tissue in adult patients if they are hyperechoic on ultrasound imaging or blush-like at unenhanced MRI; typically a small number of these lesions are tender/painful. Imaging does not demonstrate inflammation or oedema in relation to these lesions. These MRI features should suggest the diagnosis and are likely to be pathognomonic. The radiologist is often the first to suggest the diagnosis based on the
Ultrasound internal tattooing.
Couture, Olivier; Faivre, Magalie; Pannacci, Nicolas; Babataheri, Avin; Servois, Vincent; Tabeling, Patrick; Tanter, Mickael
2011-02-01
The ability of remotely tagging tissues in a controlled and three-dimensional manner during preoperative imaging could greatly help surgeons to identify targets for resection. The authors' objective is to selectively and noninvasively deposit markers under image guidance for such internal tattooing. This study describes the production of new ultrasound-inducible droplets carrying large payloads of fluorescent markers and the in vivo proof of concept of their remote and controlled deposition via focused ultrasound. The droplets are monodispersed multiple emulsions produced in a microfluidic system, consisting of aqueous fluorescein in perfluorocarbon in water. Their conversion (either by vaporization or cavitation) is performed remotely using a clinical ultrasonic imaging probe. When submitted to 5 MHz imaging pulses, the droplets vaporize in vitro at 1.4 MPa peak-negative pressure and eject their content. After several seconds, a brightly fluorescent spot (0.5 mm diameter) is observed at the focus of the transducer. Experiments in the chorioallantoique membrane of chicken eggs and chicken embryo demonstrate that the spot is stable and is easily seen by naked eye. These ultrasound-inducible multiple emulsions could be used to deliver large amounts of contrast agents, chemotherapy, and genetic materials in vivo using a conventional ultrasound scanner.
... completed. Young children may need additional preparation. When scheduling an ultrasound for yourself or your child, ask ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...
Role of ultrasound in colorectal diseases.
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.
Ultrasound biomicroscopic findings in hallerman-streiff syndrome.
Sato, Miho; Terasaki, Hiroko; Amano, Emil; Okamoto, Yoko; Miyake, Yozo
2002-01-01
To demonstrate the usefulness of ultrasound biomicroscopy in detecting the morphological changes in the lens caused by the spontaneous absorption of lens material and to detect fundus abnormalities in a patient with Hallermann-Streiff syndrome. Case report of an infant diagnosed at the age of 2 months as having Hallermann-Streiff syndrome. Spontaneous lens absorption occurred during the course of follow-up and was detected only by ultrasound biomicroscopy after the patient was prepared for cataract surgery. The changes in the anterior chamber depth and lens shapes were documented by ultrasound biomicroscopy. Retinal folds that were barely observable by conventional ophthalmoscopy because of a dense cataract were clearly shown by ultrasound biomicroscopy. Ultrasound biomicroscopy can be used to examine the lenses of eyes that are not observable with conventional optical instruments. Ultrasound biomicroscopy can also be used to study the posterior segment of microphthalmic eyes. We recommend preoperative ultrasound biomicroscopy to prevent unnecessary anesthesia and surgical preparation.
Physics and instrumentation of ultrasound.
Lawrence, John P
2007-08-01
A thorough understanding of the physics of ultrasound waves and the instrumentation will provide the user with a better understanding of the capabilities and limitations of ultrasound equipment. The ultrasound machine combines two technologies: image production (M-mode and 2-dimensional imaging) with Doppler assessment (continuous and pulse wave as well as color-flow mapping). These distinct technologies have been combined to provide the examiner with the ability to make accurate and comprehensive diagnoses and guide therapeutic intervention.
Putting ultrasound to use in food processing
USDA-ARS?s Scientific Manuscript database
Ultrasound has been applied to a wide range of food processing operations, both in research laboratories and commercially. This emerging technology has received a good deal of interest due to its green nature and nonthermal benefits, which include increased throughput, reduced cost, improved final ...
Ultrasound Molecular Imaging: Moving Towards Clinical Translation
Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.
2015-01-01
Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. PMID:25851932
Lisciandro, Gregory R; Fosgate, Geoffrey T; Fulton, Robert M
2014-01-01
Lung ultrasound is superior to lung auscultation and supine chest radiography for many respiratory conditions in human patients. Ultrasound diagnoses are based on easily learned patterns of sonographic findings and artifacts in standardized images. By applying the wet lung (ultrasound lung rockets or B-lines, representing interstitial edema) versus dry lung (A-lines with a glide sign) concept many respiratory conditions can be diagnosed or excluded. The ultrasound probe can be used as a visual stethoscope for the evaluation of human lungs because dry artifacts (A-lines with a glide sign) predominate over wet artifacts (ultrasound lung rockets or B-lines). However, the frequency and number of wet lung ultrasound artifacts in dogs with radiographically normal lungs is unknown. Thus, the primary objective was to determine the baseline frequency and number of ultrasound lung rockets in dogs without clinical signs of respiratory disease and with radiographically normal lung findings using an 8-view novel regionally based lung ultrasound examination called Vet BLUE. Frequency of ultrasound lung rockets were statistically compared based on signalment, body condition score, investigator, and reasons for radiography. Ten left-sided heart failure dogs were similarly enrolled. Overall frequency of ultrasound lung rockets was 11% (95% confidence interval, 6-19%) in dogs without respiratory disease versus 100% (95% confidence interval, 74-100%) in those with left-sided heart failure. The low frequency and number of ultrasound lung rockets observed in dogs without respiratory disease and with radiographically normal lungs suggests that Vet BLUE will be clinically useful for the identification of canine respiratory conditions. © 2014 American College of Veterinary Radiology.
Ultrasound influence on the activation step before electroless coating.
Touyeras, F; Hihn, J Y; Delalande, S; Viennet, R; Doche, M L
2003-10-01
This paper is devoted to the electroless plating of non-conductive substrates under ultrasound at 530 kHz. The ultrasonic irradiation is applied to the activation and to the plating steps. Effects are measured by following the final copper thickness obtained in 1 h of plating time, easily correlated to the average plating rate. It appears that ultrasound has a strong influence on the plating rates enhancement, and assumptions can be made that this increase could be linked to the catalyst cleaning. This is confirmed by XPS measurements.
Evaluation of the eZono 4000 with eZGuide for ultrasound-guided procedures.
Gadsden, Jeff; Latmore, Malikah; Levine, Daniel M
2015-05-01
Ultrasound-guided procedures are increasingly common in a variety of acute care settings, such as the operating room, critical care unit and emergency room. However, accurate judgment of needle tip position using traditional ultrasound technology is frequently difficult, and serious injury can result from inadvertently advancing beyond or through the target. Needle navigation is a recent innovation that allows the clinician to visualize the needle position and trajectory in real time as it approaches the target. A novel ultrasound machine has recently been introduced that is portable and designed for procedural guidance. The eZono 4000™ features an innovative needle navigation technology that is simple to use and permits the use of a wide range of commercially available needles, avoiding the inconvenience and cost of proprietary equipment. This article discusses this new ultrasound machine in the context of other currently available ultrasound machines featuring needle navigation.
Endobronchial Ultrasound (EBUS) - Update 2017.
Darwiche, Kaid; Özkan, Filiz; Wolters, Celina; Eisenmann, Stephan
2018-02-01
Endobronchial ultrasound (EBUS) has revolutionized the diagnosis of lung cancer over the last decade. This minimally invasive diagnostic method has also become increasingly important in the case of other diseases such as sarcoidosis, thereby helping to avoid unnecessary diagnostic interventions. This review article provides an update regarding EBUS and discusses current and future developments of this method. © Georg Thieme Verlag KG Stuttgart · New York.
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
Optical fiber ultrasound transmitter with electrospun carbon nanotube-polymer composite
NASA Astrophysics Data System (ADS)
Poduval, Radhika K.; Noimark, Sacha; Colchester, Richard J.; Macdonald, Thomas J.; Parkin, Ivan P.; Desjardins, Adrien E.; Papakonstantinou, Ioannis
2017-05-01
All-optical ultrasound transducers are promising for imaging applications in minimally invasive surgery. In these devices, ultrasound is transmitted and received through laser modulation, and they can be readily miniaturized using optical fibers for light delivery. Here, we report optical ultrasound transmitters fabricated by electrospinning an absorbing polymer composite directly onto the end-face of optical fibers. The composite coating consisting of an aqueous dispersion of multi-walled carbon nanotubes (MWCNTs) in polyvinyl alcohol was directly electrospun onto the cleaved surface of a multimode optical fiber and subsequently dip-coated with polydimethylsiloxane (PDMS). This formed a uniform nanofibrous absorbing mesh over the optical fiber end-face wherein the constituent MWCNTs were aligned preferentially along individual nanofibers. Infiltration of the PDMS through this nanofibrous mesh onto the underlying substrate was observed and the resulting composites exhibited high optical absorption (>97%). Thickness control from 2.3 μm to 41.4 μm was obtained by varying the electrospinning time. Under laser excitation with 11 μJ pulse energy, ultrasound pressures of 1.59 MPa were achieved at 1.5 mm from the coatings. On comparing the electrospun ultrasound transmitters with a dip-coated reference fabricated using the same constituent materials and possessing identical optical absorption, a five-fold increase in the generated pressure and wider bandwidth was observed. The electrospun transmitters exhibited high optical absorption, good elastomer infiltration, and ultrasound generation capability in the range of pressures used for clinical pulse-echo imaging. All-optical ultrasound probes with such transmitters fabricated by electrospinning could be well-suited for incorporation into catheters and needles for diagnostics and therapeutic applications.
Biophysical characterization of low-frequency ultrasound interaction with dental pulp stem cells
2013-01-01
for cell proliferation during tooth repair. Results The results demonstrate that odontoblast MDPC-23 cell numbers were significantly increased following three consecutive ultrasound treatments over a 7-day culture period as compared with sham controls underscoring the anabolic effects of ultrasound on these cells. Data show a distinct increase in cell number compared to the sham data after ultrasound treatment for intensities of 10 and 25 mW/cm2 (p < 0.05 and p < 0.01, respectively). Using finite element analysis, we demonstrated that ultrasound does indeed propagate through the mineralized layers of the teeth and into the pulp chamber where it forms a ‘therapeutic’ force field to interact with the living dental pulp cells. This allowed us to observe the pressure/intensity of the wave as it propagates throughout the tooth. A selection of time-dependent snapshots of the pressure/intensity reveal that the lower frequency waves propagate to the pulp and remain within the chamber for a while, which is ideal for cell excitation. Input frequencies and pressures of 30 kHz (70 Pa) and 45 kHz (31 kPa), respectively, with an average SPTA of up to 120 mW/cm2 in the pulp seem to be optimal and agree with the SATA intensities reported experimentally. Conclusions Our data suggest that ultrasound can be harnessed to propagate to the dental pulp region where it can interact with the living cells to promote dentine repair. Further research is required to analyze the precise physical and biological interactions of low-frequency ultrasound with the dental pulp to develop a novel non-invasive tool for dental tissue regeneration. PMID:25516801
[Ultrasound-guided peripheral catheterization].
Salleras-Duran, Laia; Fuentes-Pumarola, Concepció
2016-01-01
Peripheral catheterization is a technique that can be difficult in some patients. Some studies have recently described the use of ultrasound to guide the venous catheterization. To describe the success rate, time required, complications of ultrasound-guided peripheral venous catheterization. and patients and professionals satisfaction The search was performed in databases (Medline-PubMed, Cochrane Library, CINAHL and Cuiden Plus) for studies published about ultrasound-guided peripheral venous catheterization performed on patients that provided results on the success of the technique, complications, time used, patient satisfaction and the type of professional who performed the technique. A total of 21 studies were included. Most of them get a higher success rate 80% in the catheterization ecoguide and time it is not higher than the traditional technique. The Technical complications analyzed were arterial puncture rates and lower nerve 10%. In all studies measuring and comparing patient satisfaction in the art ecoguide is greater. Various professional groups perform the technique. The use of ultrasound for peripheral pipes has a high success rate, complications are rare and the time used is similar to that of the traditional technique. The technique of inserting catheters through ultrasound may be learned by any professional group performing venipuncture. Finally, it gets underscores the high patient satisfaction with the use of this technique. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
Measurement of tissue viscoelasticity with ultrasound
NASA Astrophysics Data System (ADS)
Greenleaf, J. F.; Alizad, A.
2017-02-01
Tissue properties such as elasticity and viscosity have been shown to be related to such tissue conditions as contraction, edema, fibrosis, and fat content among others. Magnetic Resonance Elastography has shown outstanding ability to measure the elasticity and in some cases the viscosity of tissues, especially in the liver, providing the ability to stage fibrotic liver disease similarly to biopsy. We discuss ultrasound methods of measuring elasticity and viscosity in tissues. Many of these methods are becoming widely available in the extant ultrasound machines distributed throughout the world. Some of the methods to be discussed are in the developmental stage. The advantages of the ultrasound methods are that the imaging instruments are widely available and that many of the viscoelastic measurements can be made during a short addition to the normal ultrasound examination time. In addition, the measurements can be made by ultrasound repetitively and quickly allowing evaluation of dynamic physiologic function in circumstances such as muscle contraction or artery relaxation. Measurement of viscoelastic tissue mechanical properties will become a consistent part of clinical ultrasound examinations in our opinion.
Ahmad, Junaid; Jayet, Baptiste; Hill, Philip J.; Mather, Melissa L.; Dehghani, Hamid; Morgan, Stephen P.
2018-01-01
In vivo imaging of self-illuminating bio-and chemiluminescent reporters is used to observe the physiology of small animals. However, strong light scattering by biological tissues results in poor spatial resolution of the optical imaging, which also degrades the quantitative accuracy. To overcome this challenging problem, focused ultrasound is used to modulate the light from the reporter at the ultrasound frequency. This produces an ultrasound switchable light ‘beacon’ that reduces the influence of light scattering in order to improve spatial resolution. The experimental results demonstrate that apart from light modulation at the ultrasound frequency (AC signal at 3.5 MHz), ultrasound also increases the DC intensity of the reporters. This is shown to be due to a temperature rise caused by insonification that was minimized to be within acceptable mammalian tissue safety thresholds by adjusting the duty cycle of the ultrasound. Line scans of bio-and chemiluminescent objects embedded within a scattering medium were obtained using ultrasound modulated (AC) and ultrasound enhanced (DC) signals. Lateral resolution is improved by a factor of 12 and 7 respectively, as compared to conventional CCD imaging. Two chemiluminescent sources separated by ~10 mm at ~20 mm deep inside a 50 mm thick chicken breast have been successfully resolved with an average signal-to-noise ratio of approximately 8-10 dB. PMID:29675309
Emerging Non-Cancer Applications of Therapeutic Ultrasound
O’Reilly, Meaghan A.; Hynynen, Kullervo
2015-01-01
Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer, clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programs that have great potential to impact patient care. PMID:25792225
Experimental analysis and modeling of ultrasound assisted freezing of potato spheres.
Kiani, Hossein; Zhang, Zhihang; Sun, Da-Wen
2015-09-01
In recent years, innovative methods such as ultrasound assisted freezing have been developed in order to improve the freezing process. During freezing of foods, accurate prediction of the temperature distribution, phase ratios, and process time is very important. In the present study, ultrasound assisted immersion freezing process (in 1:1 ethylene glycol-water solution at 253.15K) of potato spheres (0.02 m diameter) was evaluated using experimental, numerical and analytical approaches. Ultrasound (25 kHz, 890 W m(-2)) was irradiated for different duty cycles (DCs=0-100%). A finite volume based enthalpy method was used in the numerical model, based on which temperature and liquid fraction profiles were simulated by a program developed using OpenFOAM® CFD software. An analytical technique was also employed to calculate freezing times. The results showed that ultrasound irradiation could decrease the characteristic freezing time of potatoes. Since ultrasound irradiation increased the heat transfer coefficient but simultaneously generated heat at the surface of the samples, an optimum DC was needed for the shortest freezing time which occurred in the range of 30-70% DC. DCs higher than 70% increased the freezing time. DCs lower than 30% did not provide significant effects on the freezing time compared to the control sample. The numerical model predicted the characteristic freezing time in accordance with the experimental results. In addition, analytical calculation of characteristic freezing time exhibited qualitative agreement with the experimental results. As the numerical simulations provided profiles of temperature and water fraction within potatoes frozen with or without ultrasound, the models can be used to study and control different operation situations, and to improve the understanding of the freezing process. Copyright © 2015 Elsevier B.V. All rights reserved.
Ultrasound-Mediated Transdermal Drug Delivery: Mechanisms, Scope, and Emerging Trends
Polat, Baris E.; Hart, Douglas; Langer, Robert; Blankschtein, Daniel
2012-01-01
The use of ultrasound for the delivery of drugs to, or through, the skin is commonly known as sonophoresis or phonophoresis. The use of therapeutic and high frequencies of ultrasound (≥ 0.7 MHz) for sonophoresis (HFS) dates back to as early as the 1950s, while low-frequency sonophoresis (LFS, 20 – 100 kHz) has only been investigated significantly during the past two decades. Although HFS and LFS are similar because they both utilize ultrasound to increase the skin penetration of permeants, the mechanisms associated with each physical enhancer are different. Specifically, the location of cavitation and the extent to which each process can increase skin permeability are quite dissimilar. Although the applications of both technologies are different, they each have strengths that could allow them to improve current methods of local, regional, and systemic drug delivery. In this review, we will discuss the mechanisms associated with both HFS and LFS, specifically concentrating on the key mechanistic differences between these two skin treatment methods. Background on the relevant physics associated with ultrasound transmitted through aqueous media will also be discussed, along with implications of these phenomena on sonophoresis. Finally, a thorough review of the literature is included, dating back to the first published reports of sonophoresis, including a discussion of emerging trends in the field. PMID:21238514
Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D
2015-09-01
Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.
Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound
Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph
2012-01-01
Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone’s mechanical strength and structural parameters, i.e., bulk Young’s modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young’s modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone’s structural integrity. PMID:23976803
Borden, Mark A.; Streeter, Jason E.; Sirsi, Shashank R.; Dayton, Paul A.
2015-01-01
In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo. PMID:23981781
BBB disruption with unfocused ultrasound alone-A paradigm shift
NASA Astrophysics Data System (ADS)
Kyle, Al
2012-10-01
One paradigm for ultrasound-enabled blood brain barrier disruption uses image guided focused ultrasound and preformed microbubble agents to enable drug delivery to the brain. We propose an alternative approach: unguided, unfocused ultrasound with no adjunctive agent. Compared with the focused approach, the proposed method affects a larger region of the brain, and is aimed at treatment of regional neurological disease including glioblastoma multiforme (GBM). Avoidance of image guidance and focusing reduces cost for equipment and staff training. Avoidance of adjunctive agents also lowers cost and is enabled by a longer exposure time. Since 2004, our group has worked with two animal models, three investigators in four laboratories to safely deliver five compounds, increasing the concentration of large molecule markers in brain tissue two fold or more. Safety and effectiveness data for four studies have been presented at the Ultrasound Industry Association meetings in 2007 and 2010. This paper describes new safety and effectiveness results for a fifth study. We present evidence of delivery of large molecules - including Avastin-to the brains of a large animal model correlated with acoustic pressure, and summarize the advantages and disadvantages of this novel approach.
Automatic Cataract Hardness Classification Ex Vivo by Ultrasound Techniques.
Caixinha, Miguel; Santos, Mário; Santos, Jaime
2016-04-01
To demonstrate the feasibility of a new methodology for cataract hardness characterization and automatic classification using ultrasound techniques, different cataract degrees were induced in 210 porcine lenses. A 25-MHz ultrasound transducer was used to obtain acoustical parameters (velocity and attenuation) and backscattering signals. B-Scan and parametric Nakagami images were constructed. Ninety-seven parameters were extracted and subjected to a Principal Component Analysis. Bayes, K-Nearest-Neighbours, Fisher Linear Discriminant and Support Vector Machine (SVM) classifiers were used to automatically classify the different cataract severities. Statistically significant increases with cataract formation were found for velocity, attenuation, mean brightness intensity of the B-Scan images and mean Nakagami m parameter (p < 0.01). The four classifiers showed a good performance for healthy versus cataractous lenses (F-measure ≥ 92.68%), while for initial versus severe cataracts the SVM classifier showed the higher performance (90.62%). The results showed that ultrasound techniques can be used for non-invasive cataract hardness characterization and automatic classification. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Fiber-Optic Ultrasound Sensors for Smart Structures Applications
2000-01-25
Introduction 1 1.1 Objectives 1 1.2 Relevance to Air Force 1 1.3 Fiber Optics Ultrasound Sensors 2 2. Research Accomplishments 2 2.1 Fabry - Perot ...fiber-optic ultrasound receivers: - Fabry - Perot (FOFP) sensors, - Sagnac Ultrasound Sensor (SUS), and - Bragg-Grating Ultrasound (BGU) sensors. We...ultrasound receivers with excellent normal-incidence response can be configured as local ( Fabry - Perot ) or non-local (Sagnac) sensors. The Sagnac
Medical students benefit from the use of ultrasound when learning peripheral IV techniques.
Osborn, Scott R; Borhart, Joelle; Antonis, Michael S
2012-03-06
Recent studies support high success rates after a short learning period of ultrasound IV technique, and increased patient and provider satisfaction when using ultrasound as an adjunct to peripheral IV placement. No study to date has addressed the efficacy for instructing ultrasound-naive providers. We studied the introduction of ultrasound to the teaching technique of peripheral IV insertion on first- and second-year medical students. This was a prospective, randomized, and controlled trial. A total of 69 medical students were randomly assigned to the control group with a classic, landmark-based approach (n = 36) or the real-time ultrasound-guided group (n = 33). Both groups observed a 20-min tutorial on IV placement using both techniques and then attempted vein cannulation. Students were given a survey to report their results and observations by a 10-cm visual analog scale. The survey response rate was 100%. In the two groups, 73.9% stated that they attempted an IV previously, and 63.7% of students had used an ultrasound machine prior to the study. None had used ultrasound for IV access prior to our session. The average number of attempts at cannulation was 1.42 in either group. There was no difference between the control and ultrasound groups in terms of number of attempts (p = 0.31). In both groups, 66.7% of learners were able to cannulate in one attempt, 21.7% in two attempts, and 11.6% in three attempts. The study group commented that they felt they gained more knowledge from the experience (p < 0.005) and that it was easier with ultrasound guidance (p < 0.005). Medical students feel they learn more when using ultrasound after a 20-min tutorial to place IVs and cannulation of the vein feels easier. Success rates are comparable between the traditional and ultrasound teaching approaches.
Cancel, Limary M; Tarbell, John M; Ben-Jebria, Abdellaziz
2004-09-01
Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.
Apoptosis Induction in Cancer Cells by Ultrasound Exposure
NASA Astrophysics Data System (ADS)
Watanabe, Akihiro; Kawai, Kazuaki; Sato, Toshio; Nishimura, Hiroyuki; Kawashima, Norimichi; Takeuchi, Shinichi
2004-05-01
The methods of suppressing cancer cell proliferation by ultrasound exposure were investigated to develop a new minimally invasive cancer treatment. A stainless-steel diaphragm with a bolt-clamped Langevin-type transducer (BLT) was attached to the bottom of a water tank in the ultrasound exposure system used in this study. Cancer cells of a mouse T lymphoma (EL-4) in a flask were exposed to ultrasound under various conditions of exposure time, ultrasound frequency, ultrasound waveform, and so forth. The number of cancer cells exposed to ultrasound decreased during the culturing process. In this study, it was proved by electrophoresis, enzyme activity measurement and morphological observation that cancer cell proliferation can be suppressed by apoptosis induction in cancer cells by ultrasound exposure.
Chang, Hsin-Ning; Huang, Sheng-Teng; Yeh, Yuan-Chieh; Wang, Hsin-Shih; Wang, Tzu-Hao; Wu, Yi-Hong; Pang, Jong-Hwei S
2015-11-04
Indigo naturalis has been used to treat inflammatory diseases and dermatosis, including psoriasis, since thousands of years in China. It has been proven effective in our previous clinical studies on treating psoriasis, but the active component and the mechanism of how indigo naturalis working still needs to be clarified. Since the dysregulated angiogenesis is known to play an important role in the pathogenesis of psoriasis, the anti-angiogenic effect of indigo naturalis and tryptanthrin, a pure component of indigo naturalis, was investigated. The in vivo angiogenesis was studied by chick chorioallantoic membrane assay. The in vitro studies were performed using human vascular endothelial cells. Cell viability was determined by MTT assay. Cell cycle distribution was revealed by flow cytometry. The cellular messenger (m)RNA or protein expression level was analyzed by real-time RT-PCR or Western blot, respectively. Transwell filter migration assay and matrix gel-induced tube formation method were applied to examine the angiogenic potential. Indigo naturalis significantly inhibited the in vivo vascular endothelial growth factor (VEGF)-induced angiogenesis, as well as tryptanthrin. In vitro studies confirmed that indigo naturalis and tryptanthrin reduced the number of viable vascular endothelial cells. Tryptanthrin resulted in a cell cycle arrest and dose-dependently decreased the expressions of cyclin A, cyclin B, cyclin dependent kinase(CDK) 1 and 2, but not cyclin D and cyclin E, at both the mRNA and protein levels. The migration and tube formation of vascular endothelial cells were significantly inhibited by tryptanthrin in a dose-dependent manner. Result also showed that tryptanthrin could reduce the phosphorylated levels of both protein kinase B (PKB or Akt) and focal adhesion kinase (FAK). All together, these results demonstrated the anti-angiogenic effect of tryptanthrin, the acting component of indigo naturalis and revealed the underlying mechanism by inhibiting
Hyperemia in plantar fasciitis determined by power Doppler ultrasound.
McMillan, Andrew M; Landorf, Karl B; Gregg, Julie M; De Luca, Jason; Cotchett, Matthew P; Menz, Hylton B
2013-12-01
Cross-sectional observational study. To investigate the presence of soft tissue hyperemia in plantar fasciitis with power Doppler ultrasound. Localized hyperemia is an established feature of tendinopathy, suggesting that neurovascular in-growth may contribute to tendon-associated pain in some patients. The presence of abnormal soft tissue vascularity can be assessed with Doppler ultrasound, and a positive finding can assist with targeted treatment plans. However, very little is known regarding the presence of hyperemia in plantar fasciitis and the ability of routine Doppler ultrasound to identify vascular in-growth in the plantar fascia near its proximal insertion. This observational study included 30 participants with plantar fasciitis unrelated to systemic disease and 30 age- and sex-matched controls. Ultrasound examination was performed with a 13- to 5-MHz linear transducer, and power Doppler images were assessed by 2 blinded investigators. Hyperemia of the plantar fascia was present in 8 of 30 participants with plantar fasciitis and in 2 of 30 controls. The between-group difference for hyperemia, using a 4-point scale, was statistically significant, with participants with plantar fasciitis showing increased Doppler ultrasound signal compared to controls (Mann-Whitney U, P = .03). However, the majority of participants with plantar fasciitis with evidence of hyperemia demonstrated very mild color changes, and only 3 were found to have moderate or marked hyperemia. Mild hyperemia can occur with plantar fasciitis, but most individuals will not exhibit greater soft tissue vascularity when assessed with routine Doppler ultrasound. Clinicians treating plantar fasciitis should not consider a positive Doppler signal as essential for diagnosis of the condition but, rather, as a feature that may help to refine the treatment plan for an individual patient.
Faruch Bilfeld, Marie; Lapègue, Franck; Chiavassa Gandois, Hélène; Bayol, Marie Aurélie; Bonnevialle, Nicolas; Sans, Nicolas
2017-02-01
Acromioclavicular joint injuries are typically diagnosed by clinical and radiographic assessment with the Rockwood classification, which is crucial for treatment planning. The purpose of this study was to describe how the ultrasound findings of acromioclavicular joint injury compare with radiography and MRI findings. Forty-seven patients with suspected unilateral acromioclavicular joint injury after acute trauma were enrolled in this prospective study. All patients underwent digital radiography, ultrasound and 3T MRI. A modified Rockwood classification was used to evaluate the coracoclavicular ligaments. The classifications of acromioclavicular joint injuries diagnosed with radiography, ultrasound and MRI were compared. MRI was used as the gold standard. The agreement between the ultrasound and MRI findings was very good, with a correlation coefficient of 0.83 (95 % CI: 0.72-0.90; p < 0.0001). Ultrasound detected coracoclavicular ligament injuries with a sensitivity of 88.9 %, specificity of 90.0 %, positive predictive value of 92.3 % and negative predictive value of 85.7 %. The agreement between the ultrasound and radiography findings was poor, with a correlation coefficient of 0.69 (95 % CI: 0.51-0.82; p < 0.0001). Ultrasound is an effective examination for the diagnostic work-up of lesions of the coracoclavicular ligaments in the acute phase of an acromioclavicular injury. • Ultrasound is appropriate for acute acromioclavicular trauma due to its accessibility. • Ultrasound contributes to the diagnostic work-up of acute lesions of the coracoclavicular ligaments. • Ultrasound is appropriate in patients likely to benefit from surgical treatment. • Ultrasound could be a supplement to standard radiography in acute acromioclavicular trauma.
Dong, YiJie; Mao, MinJing; Zhan, WeiWei; Zhou, JianQiao; Zhou, Wei; Yao, JieJie; Hu, YunYun; Wang, Yan; Ye, TingJun
2018-06-01
Our goal was to assess the diagnostic efficacy of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules according to size and US features. A retrospective correlation was made with 1745 whole thyroidectomy and hemithyroidectomy specimens with preoperative US-guided FNA results. All cases were divided into 5 groups according to nodule size (≤5, 5.1-10, 10.1-15, 15.1-20, and >20 mm). For target nodules, static images and cine clips of conventional US and color Doppler were obtained. Ultrasound images were reviewed and evaluated by two radiologists with at least 5 years US working experience without knowing the results of pathology, and then agreement was achieved. The Bethesda category I rate was higher in nodules larger than 15 mm (P < .05). The diagnostic accuracy was best in nodules of 5 to 10 mm in diameter. The sensitivity, accuracy, PPV, and LR for negative US-guided FNA results were better in nodules with a size range of 5 to 15 mm. The specificity, negative predictive value (NPV), and LR for positive results and the Youden index rose with increasing nodule size. Seventeen false-positive and 60 false-negative results were found in this study. The false-negative rate rose with increasing nodule size. However, the false-positive rate was highest in the group containing the smallest nodules. Nodules with circumscribed margins and those that were nonsolid and nonhypoechoic and had no microcalcifications correlated with Bethesda I FNA results. Nodules with circumscribed margins and those that were nonsolid, heterogeneous, and nonhypoechoic and had increased vascularity correlated with false-negative FNA results. Borders correlated with Bethesda I false-negative and false-positive FNA results. Tiny nodules (≤5 mm) with obscure borders tended to yield false-positive FNA results. Large nodules (>20 mm) with several US features tended to yield false-negative FNA results. © 2017 by the American Institute of Ultrasound in Medicine.
Matar, M; Picone, O; Dalmon, C; Ayoubi, J-M
2013-09-01
To evaluate the sonographers' knowledge of the National Technical Committee of Ultrasound's recommendations concerning second trimester ultrasound. Anonymous questionnaire was sent by e-mails containing 25 questions about demographic elements, the practice of second trimester ultrasound and the recommendations of the National Technical Committee of Ultrasound about second trimester ultrasound. Six hundred and eighty-four responses were obtained. Six hundred and fifty-three upon 684 (95%) of respondents practice second trimester ultrasound and 635 upon 653 (97%) know about the existence of the report of the National Technical Committee of Ultrasound. The rates of correct answers concerning recommended biometrical images vary between 97% for the biparietal diameter and head circumference, 98% for abdominal circumference and 100% for the femur length. While for morphological images, rates vary between 52% and 100%. A subgroup analysis (whether the respondents have already read the recommendations or not) showed that those who had read the recommendations have significantly better results than those who did not. Those who have already read the recommendations have better knowledge and global knowledge can be improved. National recommendations serve to promote a policy of quality assurance of ultrasound and may be used in medicolegal issues. The societies that make recommendations should more diffuse their work and practitioners should make effort to pursue the continuing medical education and to implement the recommendations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Salmon, Margaret; Salmon, Christian; Bissinger, Alexa; Muller, Mundenga Mutendi; Gebreyesus, Alegnta; Geremew, Haimanot; Wendel, Sarah K; Wendell, Sarah; Azaza, Aklilu; Salumu, Maurice; Benfield, Nerys
2015-01-01
This paper describes design of a low cost, ultrasound gel from local products applying aspects of Human Centered Design methodology. A multidisciplinary team worked with clinicians who use ultrasound where commercial gel is cost prohibitive and scarce. The team followed the format outlined in the Ideo Took Kit. Research began by defining the challenge "how to create locally available alternative ultrasound gel for a low-resourced environment? The "End-Users," were identified as clinicians who use ultrasound in Democratic Republic of the Congo and Ethiopia. An expert group was identified and queried for possible alternatives to commercial gel. Responses included shampoo, oils, water and cornstarch. Cornstarch, while a reasonable solution, was either not available or too expensive. We then sought deeper knowledge of locally sources materials from local experts, market vendors, to develop a similar product. Suggested solutions gleaned from these interviews were collected and used to create ultrasound gel accounting for cost, image quality, manufacturing capability. Initial prototypes used cassava root flour from Great Lakes Region (DRC, Rwanda, Uganda, Tanzania) and West Africa, and bula from Ethiopia. Prototypes were tested in the field and resulting images evaluated by our user group. A final prototype was then selected. Cassava and bula at a 32 part water, 8 part flour and 4 part salt, heated, mixed then cooled was the product design of choice.
Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi
2017-01-01
Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.
Alerhand, Stephen; Meltzer, James; Tay, Ee Tein
2017-08-01
Ultrasound scan has gained attention for diagnosing appendicitis due to its avoidance of ionizing radiation. However, studies show that ultrasound scan carries inferior sensitivity to computed tomography scan. A non-diagnostic ultrasound scan could increase the time to diagnosis and appendicectomy, particularly if follow-up computed tomography scan is needed. Some studies suggest that delaying appendicectomy increases the risk of perforation. To investigate the risk of appendiceal perforation when using ultrasound scan as the initial diagnostic imaging modality in children with suspected appendicitis. We retrospectively reviewed 1411 charts of children ≤17 years old diagnosed with appendicitis at two urban academic medical centers. Patients who underwent ultrasound scan first were compared to those who underwent computed tomography scan first. In the sub-group analysis, patients who only received ultrasound scan were compared to those who received initial ultrasound scan followed by computed tomography scan. Main outcome measures were appendiceal perforation rate and time from triage to appendicectomy. In 720 children eligible for analysis, there was no significant difference in perforation rate between those who had initial ultrasound scan and those who had initial computed tomography scan (7.3% vs. 8.9%, p = 0.44), nor in those who had ultrasound scan only and those who had initial ultrasound scan followed by computed tomography scan (8.0% vs. 5.6%, p = 0.42). Those patients who had ultrasound scan first had a shorter triage-to-incision time than those who had computed tomography scan first (9.2 (IQR: 5.9, 14.0) vs. 10.2 (IQR: 7.3, 14.3) hours, p = 0.03), whereas those who had ultrasound scan followed by computed tomography scan took longer than those who had ultrasound scan only (7.8 (IQR: 5.3, 11.6) vs. 15.1 (IQR: 10.6, 20.6), p < 0.001). Children < 12 years old receiving ultrasound scan first had lower perforation rate (p = 0.01) and
Ultrasound-guided venous access for pacemakers and defibrillators.
Seto, Arnold H; Jolly, Aaron; Salcedo, Jonathan
2013-03-01
Ultrasound guidance is widely recommended to reduce the risk of complications during central venous catheter placement. However, ultrasound guidance is not commonly utilized for implanting leads for cardiac rhythm management devices. We describe our technique of ultrasound-guided pacemaker implantation, including a novel pull-through technique that allows percutaneous guidewire insertion prior to the first incision. We review the literature and recent advances in ultrasound imaging technology that may facilitate the adoption of ultrasound guidance. Ultrasound guidance provides a safe and rapid technique for extrathoracic subclavian or axillary venous lead placement. © 2012 Wiley Periodicals, Inc.
Basic physics of ultrasound imaging.
Aldrich, John E
2007-05-01
The appearance of ultrasound images depends critically on the physical interactions of sound with the tissues in the body. The basic principles of ultrasound imaging and the physical reasons for many common artifacts are described.
Chaudhari, Uddhav K; Imran, M; Manjramkar, Dhananjay D; Metkari, Siddhanath M; Sable, Nilesh P; Gavhane, Dnyaneshwar S; Katkam, Rajendra R; Sachdeva, Geetanjali; Thakur, Meenakshi H; Kholkute, Sanjeeva D
2017-02-01
Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P < 0.0002). 3D ultrasound also showed a homogeneous mass in the uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.
Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction.
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
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
NASA Astrophysics Data System (ADS)
Gray, Robert H. R.; Leslie, Thomas A.; Civale, John; Kennedy, James E.; ter Haar, Gail
2007-05-01
Real time ultrasound monitoring of tissue ablation in clinical HIFU treatments currently depends on the observation of the appearance of new hyperechoic regions within the target volume, allowing visually directed treatment. These grey-scale changes are attributed to the formation of gas or vapour bubbles. In this study, scanned track lesions have been formed in ex vivo bovine liver samples at a range of ablative intensities (free field spatial peak intensities 7 - 47 kW cm-2), and tracking speeds (1-2 mms-1). Their appearance on conventional B-mode ultrasound images has been assessed using digital imaging techniques over the first 60 seconds following HIFU exposure. The size of the lesion as seen on the ultrasound scan is compared to the macroscopic size of the lesion at dissection. It is seen that the lesion size is highly dependent on the intensity and scanning speed of the transducer. Reliable lesions can be created using scanned tracks at the lowest powers, with increased numbers of cycles, and grey-scale changes correlated strongly with the histological findings. Although not a highly sensitive indication of ablated area, ultrasound monitoring of treatment is highly specific thus confirming its clinical utility.
NASA Technical Reports Server (NTRS)
Martin, David S.; South, Donna A.; Garcia, Kathleen M.; Arbeille, Philippe
2003-01-01
Physiology of the human body in space has been a major concern for space-faring nations since the beginning of the space era. Ultrasound (US) is one of the most cost effective and versatile forms of medical imaging. As such, its use in characterizing microgravity-induced changes in physiology is being realized. In addition to the use of US in related ground-based studies, equipment has also been modified to fly in space. This involves alteration to handle the stresses of launch and different power and cooling requirements. Study protocols also have been altered to accommodate the microgravity environment. Ultrasound studies to date have shown a pattern of adaptation to microgravity that includes changes in cardiac chamber sizes and vertebral spacing. Ultrasound has been and will continue to be an important component in the investigation of physiological and, possibly, pathologic changes occurring in space or as a result of spaceflight.
Ultrasound for the Anesthesiologists: Present and Future
Terkawi, Abdullah S.; Karakitsos, Dimitrios; Elbarbary, Mahmoud; Blaivas, Michael; Durieux, Marcel E.
2013-01-01
Ultrasound is a safe, portable, relatively inexpensive, and easily accessible imaging modality, making it a useful diagnostic and monitoring tool in medicine. Anesthesiologists encounter a variety of emergent situations and may benefit from the application of such a rapid and accurate diagnostic tool in their routine practice. This paper reviews current and potential applications of ultrasound in anesthesiology in order to encourage anesthesiologists to learn and use this useful tool as an adjunct to physical examination. Ultrasound-guided peripheral nerve blockade and vascular access represent the most popular ultrasound applications in anesthesiology. Ultrasound has recently started to substitute for CT scans and fluoroscopy in many pain treatment procedures. Although the application of airway ultrasound is still limited, it has a promising future. Lung ultrasound is a well-established field in point-of-care medicine, and it could have a great impact if utilized in our ORs, as it may help in rapid and accurate diagnosis in many emergent situations. Optic nerve sheath diameter (ONSD) measurement and transcranial color coded duplex (TCCD) are relatively new neuroimaging modalities, which assess intracranial pressure and cerebral blood flow. Gastric ultrasound can be used for assessment of gastric content and diagnosis of full stomach. Focused transthoracic (TTE) and transesophageal (TEE) echocardiography facilitate the assessment of left and right ventricular function, cardiac valve abnormalities, and volume status as well as guiding cardiac resuscitation. Thus, there are multiple potential areas where ultrasound can play a significant role in guiding otherwise blind and invasive interventions, diagnosing critical conditions, and assessing for possible anatomic variations that may lead to plan modification. We suggest that ultrasound training should be part of any anesthesiology training program curriculum. PMID:24348179
Ultrasound-Diagnosed Tibia Stress Fracture: A Case Report.
Amoako, Adae; Abid, Ayesha; Shadiack, Anthony; Monaco, Robert
2017-01-01
Stress fractures are a frequent cause of lower extremity pain in athletes, and especially in runners. Plain imaging has a low sensitivity. Magnetic resonance imaging (MRI) or bone scan scintigraphy is the criterion standard, but expensive. We present the case of a young female distance runner with left shin pain. Plain radiography was unremarkable. Ultrasound showed focal hyperechoic elevation of the periosteum with irregularity over the distal tibia and increased flow on Doppler. These findings were consistent with a distal tibia stress fracture and confirmed by MRI. Examination of our case will highlight the utility of considering an ultrasound for diagnosis of tibial stress fracture.
Ultrasound-Diagnosed Tibia Stress Fracture: A Case Report
Amoako, Adae; Abid, Ayesha; Shadiack, Anthony; Monaco, Robert
2017-01-01
Stress fractures are a frequent cause of lower extremity pain in athletes, and especially in runners. Plain imaging has a low sensitivity. Magnetic resonance imaging (MRI) or bone scan scintigraphy is the criterion standard, but expensive. We present the case of a young female distance runner with left shin pain. Plain radiography was unremarkable. Ultrasound showed focal hyperechoic elevation of the periosteum with irregularity over the distal tibia and increased flow on Doppler. These findings were consistent with a distal tibia stress fracture and confirmed by MRI. Examination of our case will highlight the utility of considering an ultrasound for diagnosis of tibial stress fracture. PMID:28469488
Ultrasound molecular imaging: Moving toward clinical translation.
Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K
2015-09-01
Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Electrosynthesis of hydrogen peroxide via the reduction of oxygen assisted by power ultrasound.
González-García, José; Banks, Craig E; Sljukić, Biljana; Compton, Richard G
2007-04-01
The electrosynthesis of hydrogen peroxide using the oxygen reduction reaction has been studied in the absence and presence of power ultrasound in a non-optimized sono-electrochemical flow reactor (20 cm cathodic compartment length with 6.5 cm inner diameter) with reticulated vitreous glassy carbon electrode (30 x 40 x 10 mm, 10 ppi, 7 cm(2)cm(-3)) as the cathode. The effect of several electrochemical operational variables (pH, volumetric flow, potential) and of the sono-electrochemical parameters (ultrasound amplitude and horn-to-electrode distance) on the cumulative concentration of hydrogen peroxide and current efficiency of the electrosynthesis process have been explored. The application of power ultrasound was found to increase both the cumulative concentration of hydrogen peroxide and the current efficiency. The application of ultrasound is therefore a promising approach to the increased efficiency of production of hydrogen peroxide by electrosynthesis, even in the solutions of lower pH (<12). The results demonstrate the feasibility of at-site-of-use green synthesis of hydrogen peroxide.
Sites, Brian D; Antonakakis, John G
2009-01-01
Ultrasound guided regional anesthesia (UGRA) for peripheral nerve blockade is becoming increasingly popular. The advantage of ultrasound technology is that it affords the anesthesiologist the real time ability to visualize neural structures, needle advancement, and local anesthetic spread. Recent data suggest that UGRA generates improved success rates and reductions in performance times in comparison to traditional approaches. Further, the use of ultrasound technology in peripheral nerve blocks has provided insight into needle–nerve interactions, revealing distinct limitations of nerve stimulator techniques. Given that UGRA requires a unique set of skills, formal standards and guidelines are currently being developed by leadership societies in order to foster education and training. This review article, in a case vignette format, highlights important techniques, concepts, and limitations regarding the use of ultrasound to facilitate regional anesthesia. Clinically relevant aspects of ultrasound physics are also discussed. PMID:22915860
Chang, Ying-Ju Ruby; Perry, Julie
2017-01-01
Chronic wounds are painful and debilitating to patients, pose a clinical challenge to physicians, and impose financial burden on the health-care system. New treatment options are therefore highly sought after. Ultrasound debridement is a promising technology that functions to disperse bacterial biofilms and stimulate wound healing. In this review, we focus on low-frequency ultrasound (20-60 kHz) and summarize the findings of 25 recent studies examining ultrasound efficacy. Ultrasound debridement appears to be most effective when used 3 times a week and has the potential to decrease exudate and slough, decrease patient pain, disperse biofilms, and increase healing in wounds of various etiology. Although current studies are generally of smaller size, the results are promising and we recommend the testing of low-frequency ultrasound therapy in clinical practice on a larger scale. PMID:29026808
Influence of ultrasound on the heterogeneous Fenton-like oxidation of acetic acid.
Cihanoğlu, Aydın; Gündüz, Gönül; Dükkancı, Meral
2017-11-01
The main objective of this study is to investigate the effect of ultrasound on the heterogeneous Fenton-like oxidation of acetic acid, which is one of the most resistant carboxylic acids to oxidation. For this purpose, firstly, the degradation of acetic acid was examined by using ultrasound alone and the effects of different parameters such as: type of sonication system, ultrasonic power, and addition of H 2 O 2 were investigated on the degradation of acetic acid. There was no chemical oxygen demand (COD) reduction in the presence of sonication alone. In the presence of the heterogeneous Fenton-like oxidation process alone, at 303 K, COD reduction reached only 7.1% after 2 h of reaction. However, the combination of the heterogeneous Fenton-like oxidation process with ultrasound increased the COD reduction from 7.1% to 25.5% after 2 h of reaction in an ultrasonic bath operated at 40 kHz, while the COD reduction only increased from 7.1% to 8.9% in the ultrasonic reactor operated at 850 kHz. This result indicates that the hybrid process of ultrasound and heterogeneous Fenton-like oxidation is a promising process to degrade acetic acid.
Ultrasound of the Thyroid Gland
... the patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... has substantially grown over time Because ultrasound provides real-time images, images that are renewed continuously, it also ...
... reflect off body structures. A computer receives the waves and uses them to create a picture. Unlike with an x-ray or CT scan, this test does not use ionizing radiation. The test is done in the ultrasound ...
Mechanics of ultrasound elastography
Li, Guo-Yang
2017-01-01
Ultrasound elastography enables in vivo measurement of the mechanical properties of living soft tissues in a non-destructive and non-invasive manner and has attracted considerable interest for clinical use in recent years. Continuum mechanics plays an essential role in understanding and improving ultrasound-based elastography methods and is the main focus of this review. In particular, the mechanics theories involved in both static and dynamic elastography methods are surveyed. They may help understand the challenges in and opportunities for the practical applications of various ultrasound elastography methods to characterize the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties of both bulk and thin-walled soft materials, especially the in vivo characterization of biological soft tissues. PMID:28413350
Pulse-encoded ultrasound imaging of the vitreous with an annular array.
Silverman, Ronald H; Ketterling, Jeffrey A; Mamou, Jonathan; Lloyd, Harriet O; Filoux, Erwan; Coleman, D Jackson
2012-01-01
The vitreous body is nearly transparent both optically and ultrasonically. Conventional 10- to 12-MHz diagnostic ultrasound can detect vitreous inhomogeneities at high gain settings, but has limited resolution and sensitivity, especially outside the fixed focal zone near the retina. To improve visualization of faint intravitreal fluid/gel interfaces, the authors fabricated a spherically curved 20-MHz five-element annular array ultrasound transducer, implemented a synthetic-focusing algorithm to extend the depth-of-field, and used a pulse-encoding strategy to increase sensitivity. The authors evaluated a human subject with a recent posterior vitreous detachment and compared the annular array with conventional 10-MHz ultrasound and spectral-domain optical coherence tomography. With synthetic focusing and chirp pulse-encoding, the array allowed visualization of the formed and fluid components of the vitreous with improved sensitivity and resolution compared with the conventional B-scan. Although optical coherence tomography allowed assessment of the posterior vitreoretinal interface, the ultrasound array allowed evaluation of the entire vitreous body. Copyright 2012, SLACK Incorporated.
Zhang, Peizhi; Zhu, Zhiwei; Sun, Da-Wen
2018-05-31
Freezing is an effective way of food preservation. However, traditional freezing methods have the disadvantages of low freezing efficiency and generation of large ice crystals, leading to possible damage of food quality. Power ultrasound assisted freezing as a novel technique can effectively reduce the adverse effects during freezing process. This paper gives an overview on recent researches of power ultrasound technique to accelerate the food freezing processes and illustrates the main principles of power ultrasound assisted freezing. The effects of power ultrasound on liquid food, model solid food as well as fruit and vegetables are discussed, respectively, from the aspects of increasing freezing rate and improving microstructure. It is shown that ultrasound assisted freezing can effectively improve the freezing efficiency and promote the formation of small and evenly distributed ice crystals, resulting in better food quality. Different inherent properties of food samples affect the effectiveness of ultrasound application and optimum ultrasound parameters depend on the nature of the samples. The application of ultrasound to the food industry is more likely on certain types of food products and more efforts are still needed to realize the industrial translation of laboratory results.