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Christy K Holland

Publications and source records attributed to Christy K Holland.

8 recordsLinked to original sources
PubMed2006

Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes.

INTRODUCTION: Targeted delivery of thrombolytics to the site of occlusion is an attractive concept, with implications for the treatment of many thrombo-occlusive diseases. Ultrasound enhances thrombolysis, which can be augmented by the addition of a contrast agent. We have previously reported development of echogenic liposomes (ELIP) for targeted highlighting of structures with potential for drug and gene delivery. This study evaluated the potential of ELIP for thrombolytic loading, and the effect of ultrasound exposure of thrombolytic-loaded ELIP on thrombolytic efficacy. MATERIALS AND METHODS: Tissue-plasminogen activator (tPA) was loaded into ELIP. Echogenicity was assessed and reported as mean grayscale values. Whole porcine clots were treated with plasma, free tPA, tPA+Optison (echocontrast agent), or tPA-loaded ELIP, with and without ultrasound (1 MHz, continuous wave, 2 W/cm(2), for 2 min). Clots were weighed before and after a 30-min treatment period, and results reported as percent clot mass loss. RESULTS: tPA entrapment into ELIP was feasible with 50% entrapment, and retention of echogenicity. Treatment with tPA-loaded ELIP resulted in effective clot lysis with an effect similar to treatment with free tPA. Ultrasound exposure of tPA-loaded ELIP resulted in enhanced thrombolysis (49.5% relative improvement vs. no ultrasound). Much of the ultrasound effect appeared to be related to drug release from the tPA-ELIP complex. CONCLUSIONS: We have demonstrated entrapment of tPA into ELIP with effective clot lysis and drug release using ultrasound. Our tPA-loaded ELIP has potential for specific highlighting of clots to confirm agent delivery and help focus ultrasound therapy for targeted ultrasound-facilitated thrombolysis.

Animals↗
PubMed2006

Acoustic noise characteristics of a 4 Telsa MRI scanner.

PURPOSE: To quantify the acoustic noise characteristics of a 4 Tesla MRI scanner, and determine the effects of structural acoustics and gradient pulse excitations on the sound field so that feasible noise control measures can be developed. MATERIALS AND METHODS: Acoustic noise emissions were measured in the ear and mouth locations of a typical adult. The sound pressure measurements were acquired simultaneously with the electrical current signals of the gradient pulses. Two forms of gradient waveforms (impulsive and operating pulses) were studied. RESULTS: The sound pressure levels (SPLs) emitted by the MRI scanner operating in echo-planar imaging (EPI) mode were in the range of 120-130 decibels. Three types of sound pressure responses were observed in the EPI sequences: 1) harmonic, 2) nonharmonic, and 3) broadband. The frequency-encoding gradient pulses were the most dominant and produced generally odd-number harmonics and nonharmonics. The phase-encoding gradient pulses generated mostly even-number harmonics, and the slice-selection gradient pulses produced primarily a broadband spectrum. CONCLUSION: The operating condition acoustic spectrum can be predicted from the magnet-structural acoustic transfer functions, which are independent of imaging sequences. This finding is encouraging because it shows that it is possible to treat such noises with an active noise control application.

Acoustics↗
PubMed2006

Correlation of cavitation with ultrasound enhancement of thrombolysis.

Pulsed ultrasound, when used as an adjuvant to recombinant tissue plasminogen activator (rt-PA), has been shown to enhance thrombolysis in the laboratory as well as in clinical trials for the treatment of ischemic stroke. The exact mechanism of this enhancement has not yet been elucidated. In this work, stable and inertial cavitation (SC and IC) are investigated as possible mechanisms for this enhancement. A passive cavitation detection scheme was utilized to measure cavitation thresholds at 120 kHz (80% duty cycle, 1667 Hz pulse repetition frequency) for four host fluid and sample combinations: plasma, plasma with rt-PA, plasma with clot and plasma with clot and rt-PA. Following cavitation threshold determination, clots were exposed to pulsed ultrasound for 30 min in vitro using three separate ultrasound treatment regimes: (1) no cavitation (0.15 MPa), (2) SC alone (0.24 MPa) or (3) SC + IC combined (0.36 MPa) in the presence of rt-PA. Percent clot mass loss after each treatment was used to determine thrombolysis efficacy. The highest percent mass loss was observed in the stable cavitation regime (26%), followed by the combined stable and inertial cavitation regime (20.7%). Interestingly, the percent mass loss in clots exposed to ultrasound without cavitation (13.7%) was not statistically significantly different from rt-PA alone (13%) [p > 0.05]. Significant enhancement of thrombolysis correlates with presence of cavitation and stable cavitation appears to play a more important role in the enhancement of thrombolysis. (E-mail: ).

Animals↗
PubMed2006

Acousto-mechanical and thermal properties of clotted blood.

The efficacy of ultrasound-assisted thrombolysis as an adjunct treatment of ischemic stroke is being widely investigated. To determine the role of ultrasound hyperthermia in the process of blood clot disruption, the acousto-mechanical and thermal properties of clotted blood were measured in vitro, namely, density, speed of sound, frequency-dependent attenuation, specific heat, and thermal conductivity. The amplitude coefficient of attenuation of the clots was determined for 120 kHz, 1.0 MHz, and 3.5 MHz ultrasound at room temperature (20 +/- 2 degrees C). The attenuation coefficient ranged from 0.10 to 0.30 Np/cm in porcine clots and from 0.09 to 0.23 Np/cm in human clots. The experimentally determined values of specific heat and thermal conductivity for porcine clotted blood are (3.2 +/- 0.5) x 10(3) J/kg x K and 0.55 +/- 0.13 W/m x K, respectively, and for human clotted blood are (3.5 +/- 0.8) x 10(3) J/kg x K and 0.59 +/- 0.11 W/m x K, respectively. Measurements of the acousto-mechanical and thermal properties of clotted blood can be helpful in theoretical modeling of ultrasound hyperthermia in ultrasound-assisted thrombolysis and other high-intensity focused ultrasound applications.

Animals↗
PubMed2006

Acoustic techniques for assessing the Optison destruction threshold.

OBJECTIVE: The purpose of this study was to identify the pressure threshold for the destruction of Optison (octafluoropropane contrast agent; Amersham Health, Princeton, NJ) using a laboratory-assembled 3.5-MHz pulsed ultrasound system and a clinical diagnostic ultrasound scanner. METHODS: A 3.5-MHz focused transducer and a linear array with a center frequency of 6.9 MHz were positioned confocally and at 90 degrees to each other in a tank of deionized water. Suspensions of Optison (5-8x10(4) microbubbles/mL) were insonated with 2-cycle pulses from the 3.5-MHz transducer (peak rarefactional pressure, or Pr, from 0.0, or inactive, to 0.6 MPa) while being interrogated with fundamental B-mode imaging pulses (mechanical index, or MI,=0.04). Scattering received by the 3.5-MHz transducer or the linear array was quantified as mean backscattered intensity or mean digital intensity, respectively, and fit with exponential decay functions (Ae-kt+N, where A+N was the amplitude at time 0; N, background echogenicity; and k, decay constant). By analyzing the decay constants statistically, a pressure threshold for Optison destruction due to acoustically driven diffusion was identified. RESULTS: The decay constants determined from quantified 3.5-MHz radio frequency data and B-mode images were in good agreement. The peak rarefactional pressure threshold for Optison destruction due to acoustically driven diffusion at 3.5 MHz was 0.15 MPa (MI=0.08). Furthermore, the rate of Optison destruction increased with increasing 3.5-MHz exposure pressure output. CONCLUSIONS: Optison destruction was quantified with a laboratory-assembled 3.5-MHz ultrasound system and a clinical diagnostic ultrasound scanner. The pressure threshold for acoustically driven diffusion was identified, and 3 distinct mechanisms of ultrasound contrast agent destruction were observed with acoustic techniques.

Albumins↗
PubMed2004

In vitro characterization of liposomes and Optison by acoustic scattering at 3.5 MHz.

Liposomes are phospholipid vesicles that can encapsulate both gas and fluid. With antibody conjugation, new formulations, known as immunoliposomes, can be targeted to atheroma and other pathologic components and are, thus, being developed as novel diagnostic ultrasound (US) echo contrast agents to enhance atherosclerosis imaging. The majority of these echogenic liposomes range in diameter from 0.25 to 5.0 microm. To quantify the echogenicity of liposome suspensions of varying concentrations, the backscattering coefficient at 3.5 MHz was determined experimentally. The backscattering coefficient was also estimated theoretically as a function of air volume fraction by modeling the encapsulated air as a free air bubble and assuming single bubble scattering. For most of the liposome concentrations examined in this study (on the order of 10(8)/mL), the backscattering coefficient equals or exceeds that of Optison at the human clinical dosage (on the order of 10(4)/mL). Experimental measurement of the decrease in backscattering coefficient shows promise as a sensitive method for determining whether liposomes are left intact or destroyed during imaging; thus, helping to explore their potential as a vehicle for targeted drug delivery. In addition, the attenuation of US through liposome suspensions is negligible at 3.5 MHz relative to the attenuation through Optison (0.25 dB/cm), suggesting that liposomes have a much higher scatter-to-attenuation ratio and could be more efficient as contrast agents.

Albumins↗