Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study

Mh, Stone; Frenkel, Victor; Dromi, Sergio; Thomas, Peter; Lewis, Ryan; Li, King C.; Horne, McDonald K.; Wood, Bradford J.

doi:10.1016/j.thromres.2007.03.023

Cited by 70 publications

(63 citation statements)

References 37 publications

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“…In these same studies where tumor growth was monitored, those treated with HIFU only were found to grow at rates not significantly slower than untreated controls, providing further evidence of the non-destructive nature of these exposures. The same exposures used for thrombolysis studies similarly showed no destructive effects, both in vitro [144] and in vivo [154].…”

Section: Safety Considerationsmentioning

confidence: 73%

“…A -a schematic representation showing how non-focused ultrasound exposures using a plane wave transducer (1) are used to treat superficially, whereas a concave tranducer (2), housed in a coupling bath of degassed water (DW), can be used to place the focal zone (FZ) of the beam deeper inside the body; B -tranducer head of a dual probe showing the concave bowl therapeutic transducer for producing a focused beam and the collinear imaging tranducer for treatment planning of the exposure. This device was modified from a Sonoblate 500 (Focus Surgery, Indianapolis, IN) and used for some of the preclinical studies described in this review [57][58][59]61,[142][143][144][145][146][147][148][149]151,153,154,157,163]; C -representative lateral and vertical B mode ultrasound scans of a subcutaneous tumor in a murine flank. The two long horizontal lines indicate the focal zone (FZ) of the transducer and the shorter vertical lines, the raster (treatment) points for the exposures.…”

Section: Discussionmentioning

confidence: 99%

“…The versatility of these exposures in providing beneficial effects, in addition to enhancing extravasation, was also demonstrated in thrombolytic studies, where improved binding and penetration of tPA in whole blood clots was observed in vitro [153], which would explain increased rates of thrombolysis found in both in vitro [144] and in vivo [154] models. It has been suggested that the increase in intercellular gaps in tumors could not only enhance local interstitial transport, but that the ensuing increase in hydraulic conductivity measured in these tumors [Frenkel, unpublished] would also lead to a reduction in interstitial fluid pressure in the core of tumors, which could improve extravasation of large molecules [155].…”

Section: 32mentioning

confidence: 99%

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Ultrasound mediated delivery of drugs and genes to solid tumors

Frenkel

2008

Advanced Drug Delivery Reviews

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429

334

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It has long been shown that therapeutic ultrasound can be used effectively to ablate solid tumors, and a variety of cancers are presently being treated in the clinic using these types of ultrasound exposures. There is, however, an ever-increasing body of preclinical literature that demonstrates how ultrasound energy can also be used non-destructively for increasing the efficacy of drugs and genes for improving cancer treatment. In this review, a summary of the most important ultrasound mechanisms will be given with a detailed description of how each one can be employed for a variety of applications. This includes the manner by which acoustic energy deposition can be used to create changes in tissue permeability for enhancing the delivery of conventional agents, as well as for deploying and activating drugs and genes via specially tailored vehicles and formulations.

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Section: Safety Considerationsmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: 32mentioning

confidence: 99%

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Ultrasound mediated delivery of drugs and genes to solid tumors

Frenkel

2008

Advanced Drug Delivery Reviews

Self Cite

429

334

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“…65 FUS for the treatment of ischemic stroke, however, remains in the early preclinical phase, with in vitro and animal models having demonstrated initial feasibility. 16,61 MRgFUS has also been explored for thrombolysis in intraparenchymal hemorrhage. Results from a cadaveric animal model of intracranial hemorrhage demonstrated that FUS led to sufficient clot liquefaction to allow for needle aspiration of the lysate.…”

Section: Intracranial Thrombolysismentioning

confidence: 99%

Focused ultrasound in neurosurgery: a historical perspective

Harary

Segar

Huang

et al. 2018

Neurosurgical Focus

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Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

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“…Maxwell et al reported that histotripsy therapy using short, HIFU pulses can cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging [2,3]. Moreover, a study has shown the effectiveness of pursed HIFU in vitro and in vivo to enhance thrombolysis induced by tissue plasminogen activator (tPA) [17,18].…”

Section: Introductionmentioning

confidence: 99%

Temperature estimation of focused ultrasound exposures for stroke treatment

Hadjisavvas¹,

Damianou²

2011

JBiSE

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Introduction: in this paper a simulation model for predicting the temperature during the application of focused ultrasound (FUS) for stroke treatment using pulsed ultrasound is presented. Materials and methods: 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 Khokhlov-Zabolotskaya-Kuznetzov (KZK) model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (frequency, power, and duty factor) that maintain a temperature increase of less than 1˚C during the application of a pulse ultrasound protocol. Results: 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 shallow the target, the lower 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. Conclusions: This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, and duty factor) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model will be tested eventually during stroke clinical trials.

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Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study

Cited by 70 publications

References 37 publications

Ultrasound mediated delivery of drugs and genes to solid tumors

Ultrasound mediated delivery of drugs and genes to solid tumors

Focused ultrasound in neurosurgery: a historical perspective

Temperature estimation of focused ultrasound exposures for stroke treatment

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