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Effect of shell type on thein vivobackscatter from polymer-encapsulated microbubbles

Ultrasound in Medicine & Biology
Publication Date
DOI: 10.1016/j.ultrasmedbio.2004.07.006
  • Polymer Ultrasound Contrast Agent
  • Contrast Enhancement
  • In Vivodose Response


Abstract This study compared in vivo enhancement from four different polymer-encapsulated ultrasound (US) contrast agents. The agents were produced with a rigid shell composed of the biodegradable block copolymer poly[ d,l-lactide- co-glycolide] (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0 (i.e., increasingly hydrophobic shell compositions). Approximately the same bubble diameter (1.2 μm) and concentration (0.4 g/mL) were obtained for each agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to 0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and the time-to-peak, peak intensity, slope, area under the curve (AUC) and total duration of enhancement for each agent were compared. All agents produced marked Doppler enhancement with increasing duration from the 50:50 agent (48 ± 10 s) to the 75:25 agent (166 ± 46 s), the 85:15 agent (403 ± 83 s) and with the 100:0 agent (603 ± 93 s) lasting longest ( p < 0.02). No other parameters changed significantly, except the AUC of the 85:15 agent, which was greater than that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response curves were similar for all agents, with mean enhancement up to 20.6 ± 1.11 dB ( p = 0.17). In conclusion, contrast duration increases by an order of magnitude as the lactic acid component in the polymer-encapsulated bubbles increases and the shell, thus, becomes increasingly hydrophobic. (E-mail: [email protected])

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