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Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

ABSTRACT: The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation and radiation force. An in vitro flow model was developed to observe human whole blood clots exposed to human fresh-frozen plasma, recombinant tissue-type plasminogen activator (0, 0.32, 1.58 or 3.15 ?g/mL) and the ultrasound contrast agent Definity (2 ?L/mL). Intermittent, continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure) was used to insonify the perfusate. Ultraharmonic emissions indicative of stable cavitation were monitored with a passive cavitation detector. The clot was observed with an inverted microscope, and images were recorded with a charge-coupled device camera. The images were post-processed to determine the time-dependent clot diameter and root-mean-square velocity of the clot position. Clot lysis occurred preferentially surrounding large, resonant-sized bubbles undergoing stable oscillations. Ultraharmonic emissions from stable cavitation were found to correlate with the lytic rate. Clots were observed to translate synchronously with the initiation and cessation of the ultrasound exposure. The root-mean-square velocity of the clot correlated with the lytic rate. These data provide visual documentation of stable cavitation activity and radiation force during sub-megahertz sonothrombolysis. The observations of this study suggest that the process of clot lysis is complex, and both stable cavitation and radiation force are mechanistically responsible for this beneficial bio-effect in this in vitro model.

SUBMITTER: Bader KB

PROVIDER: S-EPMC4258471 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

Bader Kenneth B KB Gruber Matthew J MJ Holland Christy K CK

Ultrasound in medicine & biology 20141115 1

The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation and radiation force. An in vitro flow model was developed to observe human whole blood clots exposed to human fresh-frozen plasma, recombinant tissue- ...[more]

PMID: 25438846

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Project description:BACKGROUND:Oncomelania hupensis robertsoni is the sole intermediate host for Schistosoma japonicum in western China. Given the close co-evolutionary relationships between snail host and parasite, there is interest in understanding the distribution of distinct snail phylogroups as well as regional population structures. Therefore, this study focuses on these aspects in a re-emergent schistosomiasis area known to harbour representatives of two phylogroups - the Deyang-Mianyang area in Sichuan Province, China. Based on a combination of mitochondrial and nuclear DNA, the following questions were addressed: 1) the phylogeography of the two O. h. robertsoni phylogroups, 2) regional and local population structure in space and time, and 3) patterns of local dispersal under different isolation-by-distance scenarios. RESULTS:The phylogenetic analyses confirmed the existence of two distinct phylogroups within O. h. robertsoni. In the study area, phylogroups appear to be separated by a mountain range. Local specimens belonging to the respective phylogroups form monophyletic clades, indicating a high degree of lineage endemicity. Molecular clock estimations reveal that local lineages are at least 0.69-1.58 million years (My) old and phylogeographical analyses demonstrate that local, watershed and regional effects contribute to population structure. For example, Analyses of Molecular Variances (AMOVAs) show that medium-scale watersheds are well reflected in population structures and Mantel tests indicate isolation-by-distance effects along waterways. CONCLUSIONS:The analyses revealed a deep, complex and hierarchical structure in O. h. robertsoni, likely reflecting a long and diverse evolutionary history. The findings have implications for understanding disease transmission. From a co-evolutionary standpoint, the divergence of the two phylogroups raises species level questions in O. h. robertsoni and also argues for future studies relative to the distinctness of the respective parasites. The endemicity of snail lineages at the regional level supports the concept of endemic schistosomiasis areas and calls for future geospatial analyses for a better understanding of respective boundaries. Finally, local snail dispersal mainly occurs along waterways and can be best described by using cost distance, thus potentially enabling a more precise modelling of snail, and therefore, parasite dispersal.

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Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

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Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

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