Ultrasound-Enhanced rt-PA Thrombolysis in an ex vivo Porcine Carotid Artery Model

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

doi:10.1016/j.ultrasmedbio.2011.05.011

Cited by 98 publications

(97 citation statements)

References 58 publications

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“…A second PCD was aligned confocally with the blood clot sample in flow phantom. This secondary PCD, a focused 2.25-MHz transducer (595516C, Picker Roentgen GmbH, Espelkamp, Germany), has previously been utilized to detect cavitation at 120 kHz (Hitchcock et al, 2011). The PCD aperture is 1.9 cm and the focal length is 5.5 cm.…”

Section: E Ultrasound Exposure and Cavitation Detectionmentioning

confidence: 99%

“…This finding is consistent with previous investigators using UCAs to nucleate cavitation at 120 kHz. Hitchcock et al (2011) applied continuous-wave 120 kHz ultrasound and Definity V R in an ex vivo porcine carotid artery model. They found that a maximal amount of UH energy was delivered over 30 min at an acoustic pressure of 0.44 MPa (peak to peak).…”

Section: A Comparison Of Uh and Bb Thresholdsmentioning

confidence: 99%

“…Ultrasound contrast agents (UCAs) are stabilized microbubbles that can be injected into the bloodstream and have previously been used to nucleate acoustic cavitation (Rota et al, 2006;Sboros, 2008). Initial studies have demonstrated the efficacy of UET in the presence of UCAs (Molina et al, 2006;Datta et al, 2008;Hitchcock et al, 2011). These studies demonstrated UET when acoustic emissions characteristic of stable cavitation, ultraharmonics (UHs) (Ilyichev et al, 1989;Datta et al, 2008) and the subharmonic (Neppiras, 1969), were present.…”

Section: Introductionmentioning

confidence: 99%

“…Two UCAs were used to nucleate cavitation, Definity V R and echogenic liposomes (ELIP). Definity V R , a commercially available UCA, has been shown previously to nucleate stable cavitation and enhance thrombolysis (Datta et al, 2008;Brown et al, 2011;Hitchcock et al, 2011). ELIP are potential theragnostic agents for the treatment of stroke Radhakrishnan et al, 2012;Kopechek et al, 2013) with the ability to encapsulate and release rt-PA upon exposure to ultrasound.…”

Section: Introductionmentioning

confidence: 99%

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

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity V R ) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 6 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

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Section: E Ultrasound Exposure and Cavitation Detectionmentioning

confidence: 99%

Section: A Comparison Of Uh and Bb Thresholdsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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“…Each frequency spectrum was scaled to account for the energy lost due to windowing. A frequency domain comb filter was applied to the power spectrum ( Figure 3C) to extract the ultraharmonic (100 kHz bands at odd multiples of 500 kHz) and broadband 38,39 This process is depicted graphically in Figure 3.…”

Section: Ultrasound Exposure and Cavitation Detectionmentioning

confidence: 99%

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Sutton¹,

Raymond²,

Verleye³

et al. 2014

IJN

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Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

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MRI‐guided transurethral insonation of silica‐shell phase‐shift emulsions in the prostate with an advanced navigation platform

et al. 2018

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Purpose In this study, the efficacy of transurethral prostate ablation in the presence of silica‐shell ultrasound‐triggered phase‐shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated. Methods sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2O3, to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1 contrast, and temperature. In addition, non‐perfused areas (NPAs) on dynamic contrast‐enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology. Results For treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96–0.99, 0.98–0.99, and 0.91–0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion‐weighted imaging (P = 0.005) were apparent in lesions with thermal fixation. Conclusions T1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.

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Ultrasound-Enhanced rt-PA Thrombolysis in an ex vivo Porcine Carotid Artery Model

Cited by 98 publications

References 58 publications

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

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

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

MRI‐guided transurethral insonation of silica‐shell phase‐shift emulsions in the prostate with an advanced navigation platform

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